MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Cell Host and Microbe' source. Thu, 18 Mar 2010 16:38:05 +0100 http://www.medworm.com/index.php?rid=3372613&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227659%26dopt%3DAbstract Authors: Scanga CA, Flynn JL Eicosanoids can have either proinflammatory effects or anti-inflammatory effects. Tobin and colleagues use a forward genetic screen in zebrafish to identify a key eicosanoid enzyme, leukotriene A(4) hydrolase (LTA(4)H), that controls susceptibility to mycobacterial infection. They also demonstrate that polymorphisms in LTA(4)H are associated with susceptibility to mycobacteria in humans. PMID: 20227659 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3372613 Wed, 17 Mar 2010 15:38:31 +0100 3372613 http://www.medworm.com/index.php?rid=3372612&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227660%26dopt%3DAbstract Authors: Rice AP Productive transcription of the HIV-1 genome involves RNA polymerase II working in concert with the viral protein Tat and its team of cofactors in a highly orchestrated process. Now, Pagans and colleagues report that the lysine methyltransferase Set7/9-KMT7 associates with Tat to stimulate RNA polymerase II elongation of the integrated provirus. Set7/9-KMT7 also methylates Tat, and this enhances Tat function. PMID: 20227660 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3372612 Wed, 17 Mar 2010 15:38:28 +0100 3372612 http://www.medworm.com/index.php?rid=3372611&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227661%26dopt%3DAbstract Authors: Barale JC, Ménard R In this issue of Cell Host & Microbe, Iwanaga and colleagues (Iwanaga et al., 2010) report on the construction of plasmids and artificial chromosomes that are stably maintained throughout the Plasmodium life cycle. These new tools will have multiple applications, from episome-based genetic strategies to studies on telomere biology and antigenic variation. PMID: 20227661 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3372611 Wed, 17 Mar 2010 15:38:25 +0100 3372611 http://www.medworm.com/index.php?rid=3372610&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227662%26dopt%3DAbstract Authors: Chen L, Hamada S, Fujiwara M, Zhu T, Thao NP, Wong HL, Krishna P, Ueda T, Kaku H, Shibuya N, Kawasaki T, Shimamoto K Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) represents a critical first step of innate defense in plants and animals. However, maturation and transport of PRRs are not well understood. We find that the rice chitin receptor OsCERK1 interacts with Hsp90 and its cochaperone Hop/Sti1 in the endoplasmic reticulum (ER). Hop/Sti1 and Hsp90 are required for efficient transport of OsCERK1 from the ER to the plasma membrane (PM) via a pathway dependent on Sar1, a small GTPase which regulates ER-to-Golgi trafficking. Further, Hop/Sti1 and Hsp90 are present at the PM in a complex (designated the "defensome") with OsR... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3372610 Wed, 17 Mar 2010 15:38:22 +0100 3372610 http://www.medworm.com/index.php?rid=3372609&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227663%26dopt%3DAbstract Authors: Zaltsman A, Krichevsky A, Loyter A, Citovsky V Agrobacterium exports DNA into plant cells, eliciting neoplastic growths on many plant species. During this process, a Skp1-Cdc53-cullin-F-box (SCF) complex that contains the bacterial virulence F-box protein VirF facilitates genetic transformation by targeting for proteolysis proteins, the Agrobacterium protein VirE2 and the host protein VIP1, that coat the transferred DNA. However, some plant species do not require VirF for transformation. Here, we show that Agrobacterium induces expression of a plant F-box protein, which we designated VBF for VIP1-binding F-box protein, that can functionally replace VirF, regulating levels of the VirE2 and VIP1 proteins via a VBF-containing SCF complex. When expressed in Agrobacterium and expor... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3372609 Wed, 17 Mar 2010 15:38:19 +0100 3372609 http://www.medworm.com/index.php?rid=3372606&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227664%26dopt%3DAbstract Authors: Ohol YM, Goetz DH, Chan K, Shiloh MU, Craik CS, Cox JS Mycobacterium tuberculosis uses the ESX-1 secretion system to deliver virulence proteins during infection of host cells. Here we report a mechanism of posttranscriptional control of ESX-1 mediated by MycP1, a M. tuberculosis serine protease. We show that MycP1 is required for ESX-1 secretion but that, unexpectedly, genetic inactivation of MycP1 protease activity increases secretion of ESX-1 substrates. We demonstrate that EspB, an ESX-1 substrate required for secretion, is a target of MycP1 in vitro and in vivo. During macrophage infection, an inactive MycP1 protease mutant causes hyperactivation of ESX-1-stimulated innate signaling pathways. MycP1 is required for growth in mice during acute infection, while loss of its pr... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3372606 Wed, 17 Mar 2010 15:38:16 +0100 3372606 http://www.medworm.com/index.php?rid=3372605&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227665%26dopt%3DAbstract Authors: Lee K, Ambrose Z, Martin TD, Oztop I, Mulky A, Julias JG, Vandegraaff N, Baumann JG, Wang R, Yuen W, Takemura T, Shelton K, Taniuchi I, Li Y, Sodroski J, Littman DR, Coffin JM, Hughes SH, Unutmaz D, Engelman A, Kewalramani VN HIV-1 replication requires transport of nascent viral DNA and associated virion proteins, the retroviral preintegration complex (PIC), into the nucleus. Too large for passive diffusion through nuclear pore complexes (NPCs), PICs use cellular nuclear transport mechanisms and nucleoporins (NUPs), the NPC components that permit selective nuclear-cytoplasmic exchange, but the details remain unclear. Here we identify a fragment of the cleavage and polyadenylation factor 6, CPSF6, as a potent inhibitor of HIV-1 infection. When enriched in the cytoplasm, CPSF6 p... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3372605 Wed, 17 Mar 2010 15:38:12 +0100 3372605 http://www.medworm.com/index.php?rid=3372604&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227666%26dopt%3DAbstract Authors: Pagans S, Kauder SE, Kaehlcke K, Sakane N, Schroeder S, Dormeyer W, Trievel RC, Verdin E, Schnolzer M, Ott M The Tat protein of HIV-1 plays an essential role in HIV gene expression by promoting efficient elongation of viral transcripts. Posttranslational modifications of Tat fine-tune interactions of Tat with cellular cofactors and TAR RNA, a stem-loop structure at the 5' ends of viral transcripts. Here, we identify the lysine methyltransferase Set7/9 (KMT7) as a coactivator of HIV transcription. Set7/9-KMT7 associates with the HIV promoter in vivo and monomethylates lysine 51, a highly conserved residue located in the RNA-binding domain of Tat. Knockdown of Set7/9-KMT7 suppresses Tat transactivation of the HIV promoter, but does not affect the transcriptional activity of meth... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3372604 Wed, 17 Mar 2010 15:38:09 +0100 3372604 http://www.medworm.com/index.php?rid=3372603&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20227667%26dopt%3DAbstract Authors: Iwanaga S, Khan SM, Kaneko I, Christodoulou Z, Newbold C, Yuda M, Janse CJ, Waters AP The artificial chromosome represents a useful tool for gene transfer, both as cloning vectors and in chromosome biology research. To generate a Plasmodium artificial chromosome (PAC), we had to first functionally identify and characterize the parasite's centromere. A putative centromere (pbcen5) was cloned from chromosome 5 of the rodent parasite P. berghei based on a Plasmodium gene-synteny map. Plasmids containing pbcen5 were stably maintained in parasites during a blood-stage infection with high segregation efficiency, without drug pressure. pbcen5-containing plasmids were also stably maintained during parasite meiosis and mitosis in the mosquito. A linear PAC (L-PAC) was generated by inte... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3372603 Wed, 17 Mar 2010 15:38:06 +0100 3372603 http://www.medworm.com/index.php?rid=3284760&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159611%26dopt%3DAbstract Authors: Yoshimori T Autophagy has diverse roles, including defense against infection. Levine and colleagues (Orvedahl et al., 2010) provide in vivo evidence for the antiviral function of autophagy in vertebrates: autophagy protects mice against lethal Sindbis virus CNS infection by degrading viral proteins whose accumulation would otherwise cause neuronal cell death. PMID: 20159611 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284760 Thu, 18 Feb 2010 00:00:00 +0100 3284760 http://www.medworm.com/index.php?rid=3284759&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159612%26dopt%3DAbstract Authors: Pierson TC While antibodies play an important protective role during dengue virus infection, they have also been linked to more severe clinical outcomes. In this issue of Cell Host & Microbe, Zellweger and colleagues (Zellweger et al., 2010) describe the development of a murine model of antibody-enhanced dengue virus infection that provides a formal link between immune enhancement and severe disease. PMID: 20159612 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284759 Thu, 18 Feb 2010 00:00:00 +0100 3284759 http://www.medworm.com/index.php?rid=3284758&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159613%26dopt%3DAbstract Authors: van Mierlo JT, van Cleef KW, van Rij RP Virus-derived small interfering RNAs (siRNAs) are the hallmark of RNAi-based antiviral immunity. Wu and colleagues demonstrate how viral genomes can be assembled from these small RNA sequences. Their results provide an approach for virus discovery as well as important insights into how these siRNAs mediate antiviral defense. PMID: 20159613 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284758 Thu, 18 Feb 2010 00:00:00 +0100 3284758 http://www.medworm.com/index.php?rid=3284757&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159614%26dopt%3DAbstract Authors: Kafsack BF, Llinás M The application of metabolomics, the global analysis of metabolite levels, to the study of protozoan parasites has become an important tool for understanding the host-parasite relationship and holds promise for the development of direly needed therapeutics and improved diagnostics. Research advances over the past decade have opened the door for a systems biology approach to protozoan parasites with metabolomics, providing a crucial readout of metabolic activity. In this review, we highlight recent metabolomic approaches to protozoan parasites, including metabolite profiling, integration with genomics, transcription, and proteomic analysis, and the use of metabolic fingerprints for the diagnosis of parasitic infections. PMID: 20159614 [PubMed - as ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284757 Thu, 18 Feb 2010 00:00:00 +0100 3284757 http://www.medworm.com/index.php?rid=3284756&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159615%26dopt%3DAbstract Authors: Statnikov A, McVoy L, Lytkin N, Aliferis CF PMID: 20159615 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284756 Thu, 18 Feb 2010 00:00:00 +0100 3284756 http://www.medworm.com/index.php?rid=3284755&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159616%26dopt%3DAbstract Authors: Zaas AK, Chen M, Hero AO, Lucas J, Carin L, Ginsburg GS PMID: 20159616 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284755 Thu, 18 Feb 2010 00:00:00 +0100 3284755 http://www.medworm.com/index.php?rid=3284754&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159617%26dopt%3DAbstract This study demonstrates that activation of the hypothalamic-pituitary-adrenal axis controls the balance between immune defense and immunopathology and is an important component of the host response to coinfection. PMID: 20159617 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284754 Thu, 18 Feb 2010 00:00:00 +0100 3284754 http://www.medworm.com/index.php?rid=3284753&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159618%26dopt%3DAbstract Authors: Orvedahl A, Macpherson S, Sumpter R, Tallóczy Z, Zou Z, Levine B Autophagy functions in antiviral immunity. However, the ability of endogenous autophagy genes to protect against viral disease in vertebrates remains to be causally established. Here, we report that the autophagy gene Atg5 function is critical for protection against lethal Sindbis virus (SIN) infection of the mouse central nervous system. Inactivating Atg5 in SIN-infected neurons results in delayed clearance of viral proteins, increased accumulation of the cellular p62 adaptor protein, and increased cell death in neurons, but the levels of viral replication remain unaltered. In vitro, p62 interacts with SIN capsid protein, and genetic knockdown of p62 blocks the targeting of viral capsid to autophagosomes. M... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284753 Thu, 18 Feb 2010 00:00:00 +0100 3284753 http://www.medworm.com/index.php?rid=3284752&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159619%26dopt%3DAbstract Authors: Duan J, Chung H, Troy E, Kasper DL IL-17 cytokine production by the Th17 T cell subset is regulated by intestinal commmensals. We show that microbial colonization also regulates innate IL-17 production. A population of CD62L(-) gamma/delta T cells, in particular a lineage expressing the IL-1 receptor 1 (IL-1R1), can be quickly activated by microbes to produce IL-17. Antibiotic treatment and monocolonization of mice suggest that specific commensals-but not metronidazole-sensitive anaerobes like Bacteroides species-are required for maintaining IL-1R1(+) gamma/delta T cells. Signaling through the guanine nucleotide exchange factor VAV1, but not through Toll-like receptors or antigen presentation pathways, is essential for inducing IL-1R1(+) gamma/delta T cells. Furthermore, IL-1R... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284752 Thu, 18 Feb 2010 00:00:00 +0100 3284752 http://www.medworm.com/index.php?rid=3284751&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159620%26dopt%3DAbstract We report that infection with the mouse enteric pathogen, Citrobacter rodentium, increased colonic GM-CSF production and CD11c(+) DC recruitment. After infection, GM-CSF(-/-) mice had fewer mucosal CD11c(+) DCs, greater bacterial burden, increased mucosal inflammation and systemic spread of infection, decreased antibody responses, and delayed pathogen clearance. This defective mucosal response was rescued by GM-CSF administration to GM-CSF(-/-) mice and mimicked by CD11c(+) DC depletion in wild-type animals. Diminished mucosal DC numbers in infected GM-CSF(-/-) mice reflected decreased DC recruitment and survival, with the recruitment defect being related to a failure to upregulate epithelial cell production of the DC chemoattractant, CCL22. Thus, GM-CSF produced in the intestinal mucosa a... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284751 Thu, 18 Feb 2010 00:00:00 +0100 3284751 http://www.medworm.com/index.php?rid=3284750&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20159621%26dopt%3DAbstract Authors: Cui H, Wang Y, Xue L, Chu J, Yan C, Fu J, Chen M, Innes RW, Zhou JM Pathogenic microbes often modulate phytohormone physiology in the host to their advantage. We previously showed that the Pseudomonas syringae effector protein AvrB perturbs hormone signaling, as exemplified by upregulated expression of jasmonic acid response genes, and enhances plant susceptibility. Here we show that these effects of AvrB require the Arabidopsis mitogen-activated protein kinase MAP kinase 4 (MPK4), HSP90 chaperone components, and the AvrB-interacting protein, RIN4. AvrB interacts with MPK4 and the HSP90 chaperone, and AvrB induces MPK4 activation in a manner promoted by HSP90; RIN4 likely acts downstream of MPK4. These findings link Arabidopsis proteins MPK4, HSP90, and RIN4 into a pathway tha... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3284750 Thu, 18 Feb 2010 00:00:00 +0100 3284750 http://www.medworm.com/index.php?rid=3276972&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20153282%26dopt%3DAbstract Authors: Zellweger RM, Prestwood TR, Shresta S Dengue virus (DENV) causes disease ranging from dengue fever (DF), a self-limited febrile illness, to the potentially lethal dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS). DHF/DSS usually occurs in patients who have acquired DENV-reactive antibodies prior to infection, either from a previous infection with a heterologous DENV serotype or from an immune mother. Hence, it has been hypothesized that subneutralizing levels of antibodies exacerbate disease, a phenomenon termed antibody-dependent enhancement (ADE). However, given the lack of suitable animal models for DENV infection, the mechanism of ADE and its contribution to pathology remain elusive. Here we demonstrate in mice that DENV-specific antibodies can sufficiently inc... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3276972 Wed, 10 Feb 2010 00:00:00 +0100 3276972 http://www.medworm.com/index.php?rid=3229783&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114020%26dopt%3DAbstract Authors: Campellone KG Tir, a translocated effector protein from enteropathogenic E. coli (EPEC), contains two phosphotyrosines that initiate cellular signaling cascades, leading to localized actin polymerization into pedestals. A recent study now shows that two additional tyrosines within Tir recruit the inositol phosphatase SHIP2 to generate a PI(3,4)P2-enriched membrane platform that stabilizes pedestal assembly. PMID: 20114020 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229783 Thu, 21 Jan 2010 00:00:00 +0100 3229783 http://www.medworm.com/index.php?rid=3229781&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114021%26dopt%3DAbstract Authors: Vance RE Underhill and colleagues (Shimada et al., 2010) provide evidence for an intriguing link between the activity of lysozyme in the phagosome and activation of the Nlrp3 inflammasome, a cytosolic regulator of inflammation and cytokine production. The authors show that resistance to lysozyme allows Staphylococcus aureus to evade Nlrp3 activation. PMID: 20114021 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229781 Thu, 21 Jan 2010 00:00:00 +0100 3229781 http://www.medworm.com/index.php?rid=3229780&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114022%26dopt%3DAbstract Authors: Wagner H The "built-in" adjuvant in a whole-microbe vaccine potentially triggers protective immunity. Coban et al. now demonstrate that crude blood stage extract of the malaria parasite Plasmodium falciparum drives parasite-specific immune responses via Hemozoin, a byproduct of heme detoxification, functioning as a TLR9 agonist and, therefore, as a "built-in" adjuvant. PMID: 20114022 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229780 Thu, 21 Jan 2010 00:00:00 +0100 3229780 http://www.medworm.com/index.php?rid=3229779&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114023%26dopt%3DAbstract Authors: Ehlers S Focal accumulations of mononuclear cells, called granulomas, are a hallmark of mycobacterial infections. A common misconception is that granulomas are uniformly protective. In transparent zebrafish larvae infected with Mycobacterium marinum, Volkman et al. demonstrate an interaction of mycobacteria with epithelial cells that helps recruit macrophages to the granuloma as "feeder cells." PMID: 20114023 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229779 Thu, 21 Jan 2010 00:00:00 +0100 3229779 http://www.medworm.com/index.php?rid=3229778&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114024%26dopt%3DAbstract Authors: Brown GD Research into the interaction of fungi with the host has provided significant contributions to mammalian immunology. Here, I briefly review the most notable of these contributions, starting from the time of Metchnikoff, and highlight their impact on our understanding of immunity. PMID: 20114024 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229778 Thu, 21 Jan 2010 00:00:00 +0100 3229778 http://www.medworm.com/index.php?rid=3229777&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114025%26dopt%3DAbstract Authors: Smith K, Humphreys D, Hume PJ, Koronakis V Adhesion of enteropathogenic Escherichia coli to epithelial cells triggers actin-rich pedestal formation beneath the bacteria. Pedestal formation requires delivery and insertion of the bacterial translocated intimin receptor (Tir) into the host plasma membrane. The C-terminal regions in Tir, encompassing Y483 and Y511, share sequence similarity with cellular immunoreceptor tyrosine-based inhibition motifs (ITIMs), which are critical regulators of eukaryotic signaling pathways. We demonstrate that Y483 and Y511 within tandem ITIM-like sequences are essential for recruiting SHIP2, a host inositol phosphatase. SHIP2 controls condensed F-actin-pedestal formation by engaging the adaptor SHC and by generating a PI(3,4)P(2)-enriched lipid pl... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229777 Thu, 21 Jan 2010 00:00:00 +0100 3229777 http://www.medworm.com/index.php?rid=3229775&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114026%26dopt%3DAbstract Authors: Hood RD, Singh P, Hsu F, Güvener T, Carl MA, Trinidad RR, Silverman JM, Ohlson BB, Hicks KG, Plemel RL, Li M, Schwarz S, Wang WY, Merz AJ, Goodlett DR, Mougous JD The functional spectrum of a secretion system is defined by its substrates. Here we analyzed the secretomes of Pseudomonas aeruginosa mutants altered in regulation of the Hcp Secretion Island-I-encoded type VI secretion system (H1-T6SS). We identified three substrates of this system, proteins Tse1-3 (type six exported 1-3), which are coregulated with the secretory apparatus and secreted under tight posttranslational control. The Tse2 protein was found to be the toxin component of a toxin-immunity system and to arrest the growth of prokaryotic and eukaryotic cells when expressed intracellularly. In contrast, secr... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229775 Thu, 21 Jan 2010 00:00:00 +0100 3229775 http://www.medworm.com/index.php?rid=3229774&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114027%26dopt%3DAbstract Authors: Shimada T, Park BG, Wolf AJ, Brikos C, Goodridge HS, Becker CA, Reyes CN, Miao EA, Aderem A, Götz F, Liu GY, Underhill DM IL-1beta produced by phagocytes is important for protection against the mucosal pathogen Staphylococcus aureus. Processing and maturation of this cytokine requires activation of the multiprotein inflammasome complex. We observed that the bacterial cell wall component peptidoglycan (PGN) must be particulate and internalized via phagocytosis to activate NLRP3 inflammasomes and IL-1beta secretion. In the context of S. aureus infection of macrophages, we find that phagocytosis and lysozyme-based bacterial cell wall degradation are necessary to induce IL-1beta secretion. Further, an S. aureus enzyme, PGN O-acetyltransferase A, previously demonstrated to mak... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229774 Thu, 21 Jan 2010 00:00:00 +0100 3229774 http://www.medworm.com/index.php?rid=3229768&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114028%26dopt%3DAbstract Authors: Coban C, Igari Y, Yagi M, Reimer T, Koyama S, Aoshi T, Ohata K, Tsukui T, Takeshita F, Sakurai K, Ikegami T, Nakagawa A, Horii T, Nuñez G, Ishii KJ, Akira S Although whole-parasite vaccine strategies for malaria infection have regained attention, their immunological mechanisms of action remain unclear. We find that immunization of mice with a crude blood stage extract of the malaria parasite Plasmodium falciparum elicits parasite antigen-specific immune responses via Toll-like receptor (TLR) 9 and that the malarial heme-detoxification byproduct, hemozoin (HZ), but not malarial DNA, produces a potent adjuvant effect. Malarial and synthetic (s)HZ bound TLR9 directly to induce conformational changes in the receptor. The adjuvant effect of sHZ depended on its method of synthe... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229768 Thu, 21 Jan 2010 00:00:00 +0100 3229768 http://www.medworm.com/index.php?rid=3229762&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20114029%26dopt%3DAbstract Authors: Jaag HM, Pogany J, Nagy PD Viruses change rapidly due to genetic mutations, and viral RNA recombination in RNA viruses can lead to the emergence of drug-resistant or highly virulent strains. Here, we report that host Pmr1p, an ion pump that controls Ca(2+)/Mn(2+) influx into the Golgi from the cytosol, affects the frequency of viral RNA recombination and the efficiency of replication. Inactivation of PMR1 leads to an approximately 160-fold increase in RNA recombination of Tomato bushy stunt virus (TBSV) in yeast, a model host. Expression of separation-of-function mutants of Pmr1p reveals that the ability of Pmr1p to control the Mn(2+) concentration in the cytosol is a key factor in viral RNA recombination. Indeed, a high Mn(2+) concentration in a cell-free TBSV replication sys... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3229762 Thu, 21 Jan 2010 00:00:00 +0100 3229762 http://www.medworm.com/index.php?rid=3130106&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20036630%26dopt%3DAbstract Authors: Brooks CF, Johnsen H, van Dooren GG, Muthalagi M, Lin SS, Bohne W, Fischer K, Striepen B Apicomplexa are unicellular eukaryotic pathogens that carry a vestigial algal endosymbiont, the apicoplast. The physiological function of the apicoplast and its integration into parasite metabolism remain poorly understood and at times controversial. We establish that the Toxoplasma apicoplast membrane-localized phosphate translocator (TgAPT) is an essential metabolic link between the endosymbiont and the parasite cytoplasm. TgAPT is required for fatty acid synthesis in the apicoplast, but this may not be its most critical function. Further analyses demonstrate that TgAPT also functions to supply the apicoplast with carbon skeletons for additional pathways and, indirectly, with energy and ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3130106 Thu, 24 Dec 2009 00:00:00 +0100 3130106 http://www.medworm.com/index.php?rid=3000859&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917491%26dopt%3DAbstract Authors: Gupta RK, Towers GJ The study of successful versus failed zoonotic infections may provide important clues of how viral infection is naturally prevented. In this issue of Cell Host & Microbe, a collaborative group led by Frank Kirchhoff uncovers an important piece of the pandemic HIV-1 puzzle. PMID: 19917491 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000859 Wed, 18 Nov 2009 12:10:37 +0100 3000859 http://www.medworm.com/index.php?rid=3000858&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917492%26dopt%3DAbstract Authors: Wilkinson GW, Lehner PJ CPXV12 is the first poxvirus gene product demonstrated to inhibit the transporter associated with antigen processing (TAP). This cowpox virus function acts in concert with a second gene product, CPXV203, to efficiently suppress MHC class I antigen presentation and enhance in vivo virulence. PMID: 19917492 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000858 Wed, 18 Nov 2009 12:10:34 +0100 3000858 http://www.medworm.com/index.php?rid=3000857&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917493%26dopt%3DAbstract Authors: Guiton R, Dalod M Aging causes enhanced susceptibility to viral infections. Stout-Delgado et al. (2009) report increased IL-17A production but reduced type I interferon levels in old mice infected by herpes viruses. This imbalance between proinflammatory and antiviral innate cytokine responses causes immunopathology and compromises virus control, which together lead to death by liver failure. PMID: 19917493 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000857 Wed, 18 Nov 2009 12:10:32 +0100 3000857 http://www.medworm.com/index.php?rid=3000856&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917494%26dopt%3DAbstract Authors: Xayarath B, Freitag NE Riboswitches are RNA structures traditionally viewed as acting in cis to regulate downstream gene expression in bacteria. In a recent issue of Cell, Loh and colleagues report on the ability of a riboswitch to act in trans to modulate the expression of a critical bacterial virulence regulator. PMID: 19917494 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000856 Wed, 18 Nov 2009 12:10:29 +0100 3000856 http://www.medworm.com/index.php?rid=3000855&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917495%26dopt%3DAbstract Authors: Lisco A, Vanpouille C, Margolis L HIV-1 disrupts the homeostatic equilibrium between the host and coinfecting microbes, facilitating reactivation of persistent viruses and invasion by new viruses. These viruses usually accelerate HIV disease but occasionally create conditions detrimental for HIV-1. Understanding these phenomena may lead to anti-HIV-1 strategies that specifically target interactions between HIV-1 and coinfecting viruses. PMID: 19917495 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000855 Wed, 18 Nov 2009 12:10:27 +0100 3000855 http://www.medworm.com/index.php?rid=3000854&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917496%26dopt%3DAbstract Authors: Sauter D, Schindler M, Specht A, Landford WN, Münch J, Kim KA, Votteler J, Schubert U, Bibollet-Ruche F, Keele BF, Takehisa J, Ogando Y, Ochsenbauer C, Kappes JC, Ayouba A, Peeters M, Learn GH, Shaw G, Sharp PM, Bieniasz P, Hahn BH, Hatziioannou T, Kirchhoff F Vpu proteins of pandemic HIV-1 M strains degrade the viral receptor CD4 and antagonize human tetherin to promote viral release and replication. We show that Vpus from SIVgsn, SIVmus, and SIVmon infecting Cercopithecus primate species also degrade CD4 and antagonize tetherin. In contrast, SIVcpz, the immediate precursor of HIV-1, whose Vpu shares a common ancestry with SIVgsn/mus/mon Vpu, uses Nef rather than Vpu to counteract chimpanzee tetherin. Human tetherin, however, is resistant to Nef and thus poses a signific... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000854 Wed, 18 Nov 2009 12:10:24 +0100 3000854 http://www.medworm.com/index.php?rid=3000853&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917497%26dopt%3DAbstract Authors: Byun M, Verweij MC, Pickup DJ, Wiertz EJ, Hansen TH, Yokoyama WM Downregulation of MHC class I on the cell surface is an immune evasion mechanism shared by many DNA viruses, including cowpox virus. Previously, a cowpox virus protein, CPXV203, was shown to downregulate MHC class I. Here we report that CPXV12 is the only other MHC class I-regulating protein of cowpox virus and that it uses a mechanism distinct from that of CPXV203. Whereas CPXV203 retains fully assembled MHC class I by exploiting the KDEL-mediated endoplasmic reticulum retention pathway, CPXV12 binds to the peptide-loading complex and inhibits peptide loading on MHC class I molecules. Viruses deleted of both CPXV12 and CPXV203 demonstrated attenuated virulence in a CD8 T cell-dependent manner. These data demonst... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000853 Wed, 18 Nov 2009 12:10:22 +0100 3000853 http://www.medworm.com/index.php?rid=3000852&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917498%26dopt%3DAbstract Authors: Alzhanova D, Edwards DM, Hammarlund E, Scholz IG, Horst D, Wagner MJ, Upton C, Wiertz EJ, Slifka MK, Früh K Cowpox virus encodes an extensive array of putative immunomodulatory proteins, likely contributing to its wide host range, which includes zoonotic infections in humans. Unlike Vaccinia virus, cowpox virus prevents stimulation of CD8(+) T cells, a block that correlated with retention of MHC class I in the endoplasmic reticulum by the cowpox virus protein CPXV203. However, deletion of CPXV203 did not restore MHC class I transport or T cell stimulation. Here, we demonstrate the contribution of an additional viral protein, CPXV12, which interferes with MHC class I/peptide complex formation by inhibiting peptide translocation by the transporter associated with antigen pr... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000852 Wed, 18 Nov 2009 12:10:19 +0100 3000852 http://www.medworm.com/index.php?rid=3000851&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917499%26dopt%3DAbstract Authors: Stout-Delgado HW, Du W, Shirali AC, Booth CJ, Goldstein DR Morbidity and mortality associated with viral infections increase with age, although the underlying mechanisms are unclear. Here, we investigated whether aging alters inflammatory responses during systemic viral infection and thereby contributes to virus-induced death. We found that infection of aged mice with systemic herpes viruses led to rapid increases in serum IL-17, neutrophil activation, and mortality due to hepatocyte necrosis. In contrast, all young mice survived infection, displaying weaker IL-17 induction and neutrophil activation. Natural killer T (NKT) cells isolated from the livers of aged mice produced more IL-17 than did young cells, and adoptively transferred aged NKT cells induced liver injury in youn... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000851 Wed, 18 Nov 2009 12:10:17 +0100 3000851 http://www.medworm.com/index.php?rid=3000850&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917500%26dopt%3DAbstract Authors: Caplan JL, Zhu X, Mamillapalli P, Marathe R, Anandalakshmi R, Dinesh-Kumar SP Mounting an effective innate immune response against pathogens requires the rapid and global reprogramming of host cellular processes. Here we employed complementary proteomic methods to identify differentially regulated proteins early during a plant's defense response. Besides defense-related proteins, constituents of the largest category of upregulated proteins were cytoplasmic- and ER-residing molecular chaperones. Investigating the significance of upregulated ER chaperones, we find that silencing of ER-resident protein disulfide isomerases NbERp57 and NbP5 and the calreticulins NbCRT2 and NbCRT3 led to partial loss of N immune receptor-mediated defense against Tobacco mosaic virus (TMV). Furtherm... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000850 Wed, 18 Nov 2009 12:10:14 +0100 3000850 http://www.medworm.com/index.php?rid=3000849&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917501%26dopt%3DAbstract Authors: Hohl TM, Rivera A, Lipuma L, Gallegos A, Shi C, Mack M, Pamer EG Aspergillus fumigatus, a ubiquitous fungus, causes invasive disease in immunocompromised humans. Although monocytes and antigen-specific CD4 T cells contribute to defense against inhaled fungal spores, how these cells interact during infection remains undefined. Investigating the role of inflammatory monocytes and monocyte-derived dendritic cells during fungal infection, we find that A. fumigatus infection induces an influx of chemokine receptor CCR2- and Ly6C-expressing inflammatory monocytes into lungs and draining lymph nodes. Depletion of CCR2(+) cells reduced A. fumigatus conidial transport from lungs to draining lymph nodes, abolished CD4 T cell priming following respiratory challenge, and impaired pulmonar... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000849 Wed, 18 Nov 2009 12:10:11 +0100 3000849 http://www.medworm.com/index.php?rid=3000848&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19917502%26dopt%3DAbstract Authors: Dai J, Wang P, Adusumilli S, Booth CJ, Narasimhan S, Anguita J, Fikrig E Traditionally, vaccines directly target a pathogen or microbial toxin. Lyme disease, caused by Borrelia burgdorferi, is a tick-borne illness for which a human vaccine is not currently available. B. burgdorferi binds a tick salivary protein, Salp15, during transmission from the vector, and this interaction facilitates infection of mice. We now show that Salp15 antiserum significantly protected mice from B. burgdorferi infection. Salp15 antiserum also markedly enhanced the protective capacity of antibodies against B. burgdorferi antigens, such as OspA or OspC. Mice actively immunized with Salp15 were also significantly protected from tick-borne Borrelia. In vitro assays showed that Salp15 antiserum increase... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=3000848 Wed, 18 Nov 2009 12:10:08 +0100 3000848 http://www.medworm.com/index.php?rid=2912670&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837365%26dopt%3DAbstract Authors: Marcus E PMID: 19837365 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912670 Wed, 21 Oct 2009 17:48:37 +0100 2912670 http://www.medworm.com/index.php?rid=2912669&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837366%26dopt%3DAbstract Authors: Kwong PD, Mascola JR, Nabel GJ Monoclonal antibodies that effectively neutralize HIV-1 have been widely sought, yet few have been isolated. Now, technological advances in sera evaluation, B cell stimulation, microneutralization, and antibody cloning have allowed Burton and colleagues to identify two broadly neutralizing monoclonal antibodies, PG9 and PG16, which provide insights for HIV vaccine design. PMID: 19837366 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912669 Wed, 21 Oct 2009 17:48:35 +0100 2912669 http://www.medworm.com/index.php?rid=2912668&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837367%26dopt%3DAbstract Authors: Leulier F The Drosophila immune deficiency (IMD) signaling cascade regulates the IKK/NF-kappaB signaling cassette and shares striking similarities with the mammalian TNF-R1 pathway. Thevenon et al. (2009) reveal how dUSP36, a deubiquitinating enzyme of the ubiquitin-specific protease (USP) family, prevents the constitutive activation of the IMD pathway by resident gut bacteria. PMID: 19837367 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912668 Wed, 21 Oct 2009 17:48:30 +0100 2912668 http://www.medworm.com/index.php?rid=2912667&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837368%26dopt%3DAbstract Authors: Shahnazari S, Brumell JH The mechanism by which the cell responds to invading pathogens is an area of intense research. Joubert et al. (2009) have found that the phagocytic receptor CD46 is able to activate autophagy through a tripartite interaction between itself, a scaffold protein GOPC, and the autophagy inducer complex of Beclin1-VPS34. PMID: 19837368 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912667 Wed, 21 Oct 2009 17:48:27 +0100 2912667 http://www.medworm.com/index.php?rid=2912666&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837369%26dopt%3DAbstract Authors: Rossman JS, Lamb RA Viral subversion and inhibition of host cell autophagy has been documented for several viruses. In this issue of Cell Host & Microbe,Gannagé et al. (2009) show that the influenza virus M2 integral membrane protein blocks autophagosome maturation, significantly affecting host cell apoptosis. PMID: 19837369 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912666 Wed, 21 Oct 2009 17:48:25 +0100 2912666 http://www.medworm.com/index.php?rid=2912665&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837370%26dopt%3DAbstract Authors: Pitsouli C, Apidianakis Y, Perrimon N To maintain tissue homeostasis and avoid disease, epithelial cells damaged by pathogens need to be readily replenished, and this is mainly achieved by the activation of stem cells. In this Short Review, we discuss recent developments in the exciting field of host epithelia-pathogen interaction in Drosophila as well as in mammals. PMID: 19837370 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912665 Wed, 21 Oct 2009 17:48:22 +0100 2912665 http://www.medworm.com/index.php?rid=2912664&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837371%26dopt%3DAbstract Authors: Thevenon D, Engel E, Avet-Rochex A, Gottar M, Bergeret E, Tricoire H, Benaud C, Baudier J, Taillebourg E, Fauvarque MO Ubiquitin proteases remove ubiquitin monomers or polymers to modify the stability or activity of proteins and thereby serve as key regulators of signal transduction. Here, we describe the function of the Drosophila ubiquitin-specific protease 36 (dUSP36) in negative regulation of the immune deficiency (IMD) pathway controlled by the IMD protein. Overexpression of catalytically active dUSP36 ubiquitin protease suppresses fly immunity against Gram-negative pathogens. Conversely, silencing dUsp36 provokes IMD-dependent constitutive activation of IMD-downstream Jun kinase and NF-kappaB signaling pathways but not of the Toll pathway. This deregulation is lost in ax... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912664 Wed, 21 Oct 2009 17:48:20 +0100 2912664 http://www.medworm.com/index.php?rid=2912663&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837372%26dopt%3DAbstract Authors: Shivers RP, Kooistra T, Chu SW, Pagano DJ, Kim DH Microbes represent both an essential source of nutrition and a potential source of lethal infection to the nematode Caenorhabditis elegans. Immunity in C. elegans requires a signaling module comprised of orthologs of the mammalian Toll-interleukin-1 receptor (TIR) domain protein SARM, the mitogen-activated protein kinase kinase kinase (MAPKKK) ASK1, and MAPKK MKK3, which activates p38 MAPK. We determined that the SARM-ASK1-MKK3 module has dual tissue-specific roles in the C. elegans response to pathogens-in the cell-autonomous regulation of innate immunity and the neuroendocrine regulation of serotonin-dependent aversive behavior. SARM-ASK1-MKK3 signaling in the sensory nervous system also regulates egg-laying behavior that is ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912663 Wed, 21 Oct 2009 17:48:17 +0100 2912663 http://www.medworm.com/index.php?rid=2912662&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837373%26dopt%3DAbstract Authors: Shelburne CP, Nakano H, St John AL, Chan C, McLachlan JB, Gunn MD, Staats HF, Abraham SN Mast cells (MCs) are best known for eliciting harmful reactions, mostly after primary immunity has been established. Here, we report that, during footpad infection with E. coli in MC-deficient mice, as compared to their MC-sufficient counterparts, the serum antibody response is significantly diminished and less protective following passive immunization in a urinary tract infection (UTI) model in wild-type mice. MCs were found to recruit large numbers of dendritic cells (DCs) into the infected tissue site, which eventually migrated into draining lymph nodes (DLNs) during a prolonged time course. This pattern of trafficking was facilitated by MC-generated TNF, which increased the expression ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912662 Wed, 21 Oct 2009 17:48:15 +0100 2912662 http://www.medworm.com/index.php?rid=2912661&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837374%26dopt%3DAbstract Authors: Montoya D, Cruz D, Teles RM, Lee DJ, Ochoa MT, Krutzik SR, Chun R, Schenk M, Zhang X, Ferguson BG, Burdick AE, Sarno EN, Rea TH, Hewison M, Adams JS, Cheng G, Modlin RL Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. We investigated the regulation of these key functions in human blood-derived macrophages. Interleukin-10 (IL-10) induced the phagocytic pathway, including the C-type lectin CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxidized low-density lipoprotein. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The different... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912661 Wed, 21 Oct 2009 17:48:12 +0100 2912661 http://www.medworm.com/index.php?rid=2912660&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837375%26dopt%3DAbstract We report here that the engagement of CD46, a ubiquitous human surface receptor able to bind several different pathogens, is sufficient to induce autophagy. CD46-Cyt-1, one of the two C-terminal splice variants of CD46, is linked to the autophagosome formation complex VPS34/Beclin1 via its interaction with the scaffold protein GOPC. Measles virus and group A Streptococcus, two CD46-binding pathogens, induce autophagy through a CD46-Cyt-1/GOPC pathway. Thus, upon microorganism recognition, a cell surface pathogen receptor can directly trigger autophagy, a critical step to control infection. PMID: 19837375 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912660 Wed, 21 Oct 2009 17:48:10 +0100 2912660 http://www.medworm.com/index.php?rid=2912659&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837376%26dopt%3DAbstract Authors: Gannagé M, Dormann D, Albrecht R, Dengjel J, Torossi T, Rämer PC, Lee M, Strowig T, Arrey F, Conenello G, Pypaert M, Andersen J, García-Sastre A, Münz C Influenza A virus is an important human pathogen causing significant morbidity and mortality every year and threatening the human population with epidemics and pandemics. Therefore, it is important to understand the biology of this virus to develop strategies to control its pathogenicity. Here, we demonstrate that influenza A virus inhibits macroautophagy, a cellular process known to be manipulated by diverse pathogens. Influenza A virus infection causes accumulation of autophagosomes by blocking their fusion with lysosomes, and one viral protein, matrix protein 2, is necessary and sufficient for this inhib... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912659 Wed, 21 Oct 2009 17:48:07 +0100 2912659 http://www.medworm.com/index.php?rid=2912658&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19837377%26dopt%3DAbstract Authors: Mehlhop E, Nelson S, Jost CA, Gorlatov S, Johnson S, Fremont DH, Diamond MS, Pierson TC Virus neutralization is governed by the number of antibodies that bind a virion during the cellular entry process. Cellular and serum factors that interact with antibodies have the potential to modulate neutralization potency. Although the addition of serum complement can increase the neutralizing activity of antiviral antibodies in vitro, the mechanism and significance of this augmented potency in vivo remain uncertain. Herein, we show that the complement component C1q increases the potency of antibodies against West Nile virus by modulating the stoichiometric requirements for neutralization. The addition of C1q does not result in virolysis but instead reduces the number of antibodies that... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2912658 Wed, 21 Oct 2009 17:48:05 +0100 2912658 http://www.medworm.com/index.php?rid=2797602&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748460%26dopt%3DAbstract Authors: Wright GD In an era of increasing antibiotic resistance, growing clinical need for new drugs, and few lead molecules, new research is helping to identify new targets and the mechanism of action of lead molecules. PMID: 19748460 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797602 Wed, 16 Sep 2009 13:30:26 +0100 2797602 http://www.medworm.com/index.php?rid=2797601&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748461%26dopt%3DAbstract Authors: Ramilo O, Mejías A Instead of focusing on the pathogen, in a paradigm shift, Zaas et al. (2009) identified host gene profiles as a strategy for diagnosis of respiratory infections. Application of host gene profiles offers tremendous possibilities for identification of diagnostic signatures, markers of disease severity, and eventually, prognostic indicators in the clinical setting. PMID: 19748461 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797601 Wed, 16 Sep 2009 13:30:24 +0100 2797601 http://www.medworm.com/index.php?rid=2797600&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748462%26dopt%3DAbstract Authors: Fabri M, Modlin RL Recent discoveries have revealed the importance of the vitamin D-dependent generation of antimicrobial peptides in human host defense against Mycobacterium tuberculosis. Now, Yuk et al. (2009) show how vitamin D induces autophagy and mediates colocalization of Mycobacterium tuberculosis and antimicrobial peptides within an autophagolysosome, leading to killing of the bacterium. PMID: 19748462 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797600 Wed, 16 Sep 2009 13:30:21 +0100 2797600 http://www.medworm.com/index.php?rid=2797599&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748463%26dopt%3DAbstract Authors: Ferrandon D To deal with an infection, the organism resorts to nonmutually exclusive strategies: resistance, that is, neutralization or destruction of the pathogen; or tolerance, the ability to withstand damages inflicted by the pathogen or by host defense. In this issue of Cell Host & Microbe, Shinzawa et al. (2009) identify p38-mediated phagocytic encapsulation as a potential tolerance mechanism. PMID: 19748463 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797599 Wed, 16 Sep 2009 13:30:19 +0100 2797599 http://www.medworm.com/index.php?rid=2797598&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748464%26dopt%3DAbstract Authors: Muratori C, Cavallin LE, Krätzel K, Tinari A, De Milito A, Fais S, D'Aloja P, Federico M, Vullo V, Fomina A, Mesri EA, Superti F, Baur AS The HIV Nef protein mediates endocytosis of surface receptors that correlates with disease progression, but the link between this Nef function and HIV pathogenesis is not clear. Here, we report that Nef-mediated activation of membrane trafficking is bidirectional, connecting endocytosis with exocytosis as occurs in activated T cells. Nef expression induced an extensive secretory activity in infected and, surprisingly, also in noninfected T cells, leading to the massive release of microvesicle clusters, a phenotype observed in vitro and in 36%-87% of primary CD4 T cells from HIV-infected individuals. Consistent with exocytosis in noninfe... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797598 Wed, 16 Sep 2009 13:30:17 +0100 2797598 http://www.medworm.com/index.php?rid=2797597&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748465%26dopt%3DAbstract Authors: Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, Lee ZW, Lee SH, Kim JM, Jo EK Autophagy and vitamin D3-mediated innate immunity have been shown to confer protection against infection with intracellular Mycobacterium tuberculosis. Here, we show that these two antimycobacterial defenses are physiologically linked via a regulatory function of human cathelicidin (hCAP-18/LL-37), a member of the cathelicidin family of antimicrobial proteins. We show that 1,25-dihydroxyvitamin D3 (1,25D3), the active form of vitamin D, induced autophagy in human monocytes via cathelicidin, which activated transcription of the autophagy-related genes Beclin-1 and Atg5. 1,25D3 also induced the colocalization of mycobacterial phagosomes with autophagosomes in human macrophages in a cathelicidin-depen... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797597 Wed, 16 Sep 2009 13:30:15 +0100 2797597 http://www.medworm.com/index.php?rid=2797596&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748466%26dopt%3DAbstract Authors: Shinzawa N, Nelson B, Aonuma H, Okado K, Fukumoto S, Miura M, Kanuka H Hosts employ a combination of two distinct yet compatible strategies to defend themselves against parasites: resistance, the ability to limit parasite burden, and tolerance, the ability to limit damage caused by a given parasite burden. Animals typically exhibit considerable genetic variation in resistance to a variety of pathogens; however, little is known about whether animals can evolve tolerance. Using a bacterial infection model in Drosophila, we uncovered a p38 MAP kinase-mediated mechanism of tolerance to intracellular bacterial infection as measured by the extent to which the host's survival rate increased or was maintained despite increasing bacterial burden. This increased survival was conferred p... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797596 Wed, 16 Sep 2009 13:30:12 +0100 2797596 http://www.medworm.com/index.php?rid=2797595&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748467%26dopt%3DAbstract Authors: Li Z, Dugan AS, Bloomfield G, Skelton J, Ivens A, Losick V, Isberg RR The amoeba Dictyostelium discoideum can support replication of Legionella pneumophila. Here we identify the dupA gene, encoding a putative tyrosine kinase/dual-specificity phosphatase, in a screen for D. discoideum mutants altered in allowing L. pneumophila intracellular replication. Inactivation of dupA resulted in depressed L. pneumophila growth and sustained hyperphosphorylation of the amoebal MAP kinase ERK1, consistent with loss of a phosphatase activity. Bacterial challenge of wild-type amoebae induced dupA expression and resulted in transiently increased ERK1 phosphorylation, suggesting that dupA and ERK1 are part of a response to bacteria. Indeed, over 500 of the genes misregulated in the dupA(-) mut... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797595 Wed, 16 Sep 2009 13:30:10 +0100 2797595 http://www.medworm.com/index.php?rid=2797594&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748468%26dopt%3DAbstract Authors: Chong R, Swiss R, Briones G, Stone KL, Gulcicek EE, Agaisse H The actin-based motility of the intracellular pathogen Listeria monocytogenes relies on ActA, a bacterial factor with a structural domain allowing it to mimic the actin nucleation-promoting activity of host cell proteins of the WASP/WAVE family. Here, we used an RNAi-based genetic approach in combination with computer-assisted image analysis to investigate the role of host factors in L. monocytogenes cell-to-cell spread. We showed that the host cell serine/threonine kinase CK2 is required for efficient actin tail formation by L. monocytogenes. Furthermore, CK2-mediated phosphorylation of ActA regulated its affinity for the actin-nucleating ARP2/3 complex, as is the case for CK2-mediated phosphorylation of WASP and W... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797594 Wed, 16 Sep 2009 13:30:08 +0100 2797594 http://www.medworm.com/index.php?rid=2797593&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19748469%26dopt%3DAbstract Authors: Goodman AL, McNulty NP, Zhao Y, Leip D, Mitra RD, Lozupone CA, Knight R, Gordon JI The human gut microbiota is a metabolic organ whose cellular composition is determined by a dynamic process of selection and competition. To identify microbial genes required for establishment of human symbionts in the gut, we developed an approach (insertion sequencing, or INSeq) based on a mutagenic transposon that allows capture of adjacent chromosomal DNA to define its genomic location. We used massively parallel sequencing to monitor the relative abundance of tens of thousands of transposon mutants of a saccharolytic human gut bacterium, Bacteroides thetaiotaomicron, as they established themselves in wild-type and immunodeficient gnotobiotic mice, in the presence or absence of other human g... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2797593 Wed, 16 Sep 2009 13:30:05 +0100 2797593 http://www.medworm.com/index.php?rid=2713287&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683674%26dopt%3DAbstract Authors: Voinnet O In plants and invertebrates, small silencing RNAs function in antiviral defense and developmental patterning through pathways that were so far considered genetically distinct. In a recent issue of Cell, Sabin and colleagues report the identification of Drosophila Ars2, a protein required for both these small RNA-mediated functions. PMID: 19683674 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713287 Wed, 19 Aug 2009 23:00:00 +0100 2713287 http://www.medworm.com/index.php?rid=2713286&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683675%26dopt%3DAbstract Authors: Hilbi H Shigella flexneri and other invasive bacteria rupture the phagosome membrane and escape to the host cytoplasm. Now, Dupont et al. address the fate and signaling functions of pathogen vacuole remnants and show that these membrane fragments trigger host-cell-signaling responses, including polyubiquitination, autophagy, and pyroptosis. PMID: 19683675 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713286 Wed, 19 Aug 2009 23:00:00 +0100 2713286 http://www.medworm.com/index.php?rid=2713285&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683676%26dopt%3DAbstract Authors: Denkers EY We do not live in a sterile environment, but instead we are intimately associated with our commensal microbiota. Benson et al. (2009) suggest that host sensing of these microbes takes a pivotal role in getting the immune system up and running in response to a major intestinal parasite. PMID: 19683676 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713285 Wed, 19 Aug 2009 23:00:00 +0100 2713285 http://www.medworm.com/index.php?rid=2713284&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683677%26dopt%3DAbstract Authors: Welchman DP, Aksoy S, Jiggins F, Lemaitre B The Jacques Monod conference "Insect Immunity in Action: From Fundamental Mechanisms of Host Defense to Resistance Against Infections in Nature," organized by Ulrich Theopold (Stockholm University, Sweden) and Dominique Ferrandon (CNRS, France), was held in May 2009 in Aussois, France. Here, we review key topics and concepts that were presented and highlight emerging trends in the field of insect immunity. PMID: 19683677 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713284 Wed, 19 Aug 2009 23:00:00 +0100 2713284 http://www.medworm.com/index.php?rid=2713283&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683678%26dopt%3DAbstract Authors: Roux A, Payne SM, Gilmore MS Bacterial-sensing circuits may be triggered by molecules originating from the environment (e.g., nutrients and chemoattractants). Bacteria also actively probe the environment for information by releasing molecular probes to measure conditions beyond the cell surface: a process known as telesensing. Perceiving the environment beyond is achieved by sensing environmentally induced changes in those probes, as occurs when a siderophore chelates an iron atom or a quorum-sensing signal is inactivated by a specific enzyme or adsorbent. This information, captured by chemical and physical changes induced in specifically produced molecules transiting through the environment, enables bacteria to mount a contextually appropriate response. PMID: 19683678 [Pu... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713283 Wed, 19 Aug 2009 23:00:00 +0100 2713283 http://www.medworm.com/index.php?rid=2713282&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683679%26dopt%3DAbstract Authors: Müller AJ, Hoffmann C, Galle M, Van Den Broeke A, Heikenwalder M, Falter L, Misselwitz B, Kremer M, Beyaert R, Hardt WD In the healthy intestinal mucosa, homeostasis between the immune system and commensal microflora prevents detrimental inflammatory responses. Infection with acute enteropathogens such as Salmonella enterica serovar Typhimurium disturbs this homeostasis and triggers inflammation, but the underlying mechanisms are poorly understood. We found that bacterial delivery or ectopic expression of the S. Typhimurium type III effector protein SopE, a known activator of host cellular Rho GTPases, led to proinflammatory caspase-1 activation and consequent maturation and secretion of the cytokine IL-1beta. In vivo, SopE triggered mucosal inflammation in wild-type but ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713282 Wed, 19 Aug 2009 23:00:00 +0100 2713282 http://www.medworm.com/index.php?rid=2713281&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683680%26dopt%3DAbstract Authors: Dupont N, Lacas-Gervais S, Bertout J, Paz I, Freche B, Van Nhieu GT, van der Goot FG, Sansonetti PJ, Lafont F Intracellular pathogens like Shigella flexneri enter host cells by phagocytosis. Once inside, the pathogen breaks the vacuolar membrane for cytosolic access. The fate and function of the vacuolar membrane remnants are not clear. Examining Shigella-infected nonmyeloid cells, we observed that proteins associated with vacuolar membrane remnants are polyubiquinated, recruit the autophagy marker LC3 and adaptor p62, and are targeted to autophagic degradation. Further, inflammasome components and caspase-1 were localized to these membranes and correlated with dampened inflammatory response and necrotic cell death. In Atg4B mutant cells in which autophagosome maturation is bl... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713281 Wed, 19 Aug 2009 23:00:00 +0100 2713281 http://www.medworm.com/index.php?rid=2713280&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683681%26dopt%3DAbstract Authors: Kong L, Sun L, Zhang H, Liu Q, Liu Y, Qin L, Shi G, Hu JH, Xu A, Sun YP, Li D, Shi YF, Zang JW, Zhu J, Chen Z, Wang ZG, Ge BX Retinoic acid-inducible gene-I (RIG-I) plays an important role in antiviral response by recognizing double-stranded RNA. Here we demonstrate an unanticipated role of RIG-I in Toll-like receptor (TLR)-stimulated phagocytosis. Stimulation with lipopolysaccharide (LPS), a ligand of TLR4, induced the expression of RIG-I in macrophages. Depletion of RIG-I by RNAi or gene targeting inhibited the LPS-induced phagocytosis of bacteria. Cellular processes involved in phagocytosis, such as small GTPase Cdc42/Rac1 activation, actin polymerization, and actin-regulator Arp2/3 recruitment, were also impaired in RIG-I-deficient macrophages activated by LPS. Moreover, R... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713280 Wed, 19 Aug 2009 23:00:00 +0100 2713280 http://www.medworm.com/index.php?rid=2713279&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683682%26dopt%3DAbstract Authors: Panchal RG, Bradfute SB, Peyser BD, Warfield KL, Ruthel G, Lane D, Kenny TA, Anderson AO, Raschke WC, Bavari S Ebola virus (EBOV) infection of humans is a lethal but accidental dead-end event. Understanding resistance to EBOV in other species may help establish the basis of susceptibility differences among its hosts. Although rodents are resistant to EBOV, a murine-adapted variant is lethal when injected intraperitoneally into mice. We find that mice expressing reduced levels of the tyrosine phosphatase CD45 are protected against EBOV, whereas wild-type, CD45-deficient, or enzymatically inactive CD45-expressing mice succumbed to infection. Protection was dependent on CD8(+) T cells and interferon gamma. Reduced CD45-expressing mice retained greater control of gene expression a... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713279 Wed, 19 Aug 2009 23:00:00 +0100 2713279 http://www.medworm.com/index.php?rid=2713278&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683683%26dopt%3DAbstract Authors: Stolp B, Reichman-Fried M, Abraham L, Pan X, Giese SI, Hannemann S, Goulimari P, Raz E, Grosse R, Fackler OT HIV-1 Nef is a key factor in AIDS pathogenesis. Here, we report that Nef potently inhibits motility of fibroblasts and chemotaxis of HIV-1-infected primary human T lymphocytes toward the chemokines SDF-1alpha, CCL-19, and CCL-21 ex vivo. Furthermore, Nef inhibits guided motility of zebrafish primordial germ cells toward endogenous SDF-1a in vivo. These migration defects result from Nef-mediated inhibition of the actin remodeling normally triggered by migratory stimuli. Nef strongly induces phosphorylation of cofilin, inactivating this evolutionarily conserved actin-depolymerizing factor that promotes cell motility when unphosphorylated. Nef-dependent cofilin deregulatio... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713278 Wed, 19 Aug 2009 23:00:00 +0100 2713278 http://www.medworm.com/index.php?rid=2713277&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19683684%26dopt%3DAbstract Authors: Benson A, Pifer R, Behrendt CL, Hooper LV, Yarovinsky F Toxoplasma gondii is a universally distributed pathogen that infects over one billion people worldwide. Host resistance to this protozoan parasite depends on a Th1 immune response with potent production of the cytokines interleukin-12 and interferon gamma. Although Toll-like receptor 11 (TLR11) plays a major role in controlling Th1 immunity to this pathogen in mice, this innate immune receptor is nonfunctional in humans, and the mechanisms of TLR11-independent sensing of T. gondii remain elusive. Here, we show that oral infection by T. gondii triggers a TLR11-independent but MyD88-dependent Th1 response that is impaired in TLR2xTLR4 double knockout and TLR9 single knockout mice. These mucosal innate and adaptive immune re... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2713277 Wed, 19 Aug 2009 23:00:00 +0100 2713277 http://www.medworm.com/index.php?rid=2692017&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19664979%26dopt%3DAbstract Authors: Zaas AK, Chen M, Varkey J, Veldman T, Hero AO, Lucas J, Huang Y, Turner R, Gilbert A, Lambkin-Williams R, Oien NC, Nicholson B, Kingsmore S, Carin L, Woods CW, Ginsburg GS Acute respiratory infections (ARIs) are a common reason for seeking medical attention, and the threat of pandemic influenza will likely add to these numbers. Using human viral challenge studies with live rhinovirus, respiratory syncytial virus, and influenza A, we developed peripheral blood gene expression signatures that distinguish individuals with symptomatic ARIs from uninfected individuals with >95% accuracy. We validated this "acute respiratory viral" signature-encompassing genes with a known role in host defense against viral infections-across each viral challenge. We also validated the signature i... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2692017 Tue, 04 Aug 2009 23:00:00 +0100 2692017 http://www.medworm.com/index.php?rid=2627491&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616759%26dopt%3DAbstract Authors: Connolly LE, Cox JS Global reprogramming of bacterial gene expression in response to nutritional stress, the stringent response, is well studied in E. coli. Now Stallings et al. report that Mycobacterium tuberculosis employs a different strategy involving the general transcription factor CarD for growth control and persistence in response to stresses encountered during infection. PMID: 19616759 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627491 Wed, 22 Jul 2009 23:00:00 +0100 2627491 http://www.medworm.com/index.php?rid=2627489&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616760%26dopt%3DAbstract Authors: Scott P Leishmaniasis is a chronic infection in which intracellular parasites avoid destruction by the immune system. Using intravital imaging, Filipe-Santos et al. (2009) demonstrate that some parasitized dendritic cells receive much less attention than others during their choreographed dance with T cells, suggesting that these "wallflowers" could allow for parasite survival. PMID: 19616760 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627489 Wed, 22 Jul 2009 23:00:00 +0100 2627489 http://www.medworm.com/index.php?rid=2627488&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616761%26dopt%3DAbstract Authors: Legrand N, Ploss A, Balling R, Becker PD, Borsotti C, Brezillon N, Debarry J, de Jong Y, Deng H, Di Santo JP, Eisenbarth S, Eynon E, Flavell RA, Guzman CA, Huntington ND, Kremsdorf D, Manns MP, Manz MG, Mention JJ, Ott M, Rathinam C, Rice CM, Rongvaux A, Stevens S, Spits H, Strick-Marchand H, Takizawa H, van Lent AU, Wang C, Weijer K, Willinger T, Ziegler P Over 800 million people worldwide are infected with hepatitis viruses, human immunodeficiency virus (HIV), and malaria, resulting in more than 5 million deaths annually. Here we discuss the potential and challenges of humanized mouse models for developing effective and affordable therapies and vaccines, which are desperately needed to combat these diseases. PMID: 19616761 [PubMed - in process] (Source: Cell Host and Mic... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627488 Wed, 22 Jul 2009 23:00:00 +0100 2627488 http://www.medworm.com/index.php?rid=2627487&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616762%26dopt%3DAbstract Authors: Vance RE, Isberg RR, Portnoy DA The dominant conceptual framework for understanding innate immunity has been that host cells respond to evolutionarily conserved molecular features of pathogens called pathogen-associated molecular patterns (PAMPs). Here, we propose that PAMPs should be understood in the context of how they are naturally presented by pathogens. This can be experimentally challenging, since pathogens, almost by definition, bypass host defense. Nevertheless, in this review, we explore the idea that the immune system responds to PAMPs in the context of additional signals that derive from common "patterns of pathogenesis" employed by pathogens to infect, multiply within, and spread among their hosts. PMID: 19616762 [PubMed - in process] (Source: Cell Host and Mi... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627487 Wed, 22 Jul 2009 23:00:00 +0100 2627487 http://www.medworm.com/index.php?rid=2627486&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616763%26dopt%3DAbstract Authors: Filipe-Santos O, Pescher P, Breart B, Lippuner C, Aebischer T, Glaichenhaus N, Späth GF, Bousso P CD4 T helper cells play a central role in the control of infection by intracellular parasites. How efficiently pathogen-specific CD4 T cells detect infected cells in vivo is unclear. Here, we employed intravital two-photon imaging to examine the behavior of pathogen-specific CD4 T cells at the site of Leishmania major infection. While activated CD4 T cells enter the inflamed tissue irrespective of their antigen specificity, pathogen-specific T cells preferentially decelerated and accumulated in infected regions of the dermis. Antigen recognition by CD4 T cells was heterogeneous, involving both stable and dynamic contacts with infected phagocytes. However, not all infected cel... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627486 Wed, 22 Jul 2009 23:00:00 +0100 2627486 http://www.medworm.com/index.php?rid=2627485&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616764%26dopt%3DAbstract Authors: Gao M, Wang X, Wang D, Xu F, Ding X, Zhang Z, Bi D, Cheng YT, Chen S, Li X, Zhang Y Upon recognition of bacterial flagellin, the plant receptor FLS2 heterodimerizes with brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1) and activates plant defense responses. Because constitutive activation of defense responses is detrimental, plant resistance signaling pathways must be negatively controlled, although the mechanisms involved are unclear. We identified Arabidopsis BIR1 as a BAK1-interacting receptor-like kinase. Knocking out BIR1 leads to extensive cell death, activation of constitutive defense responses, and impairment in the activation of MPK4, a negative regulator of plant resistance (R) protein signaling, by flagellin. sobir1-1, a mutant obtained in a screen ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627485 Wed, 22 Jul 2009 23:00:00 +0100 2627485 http://www.medworm.com/index.php?rid=2627484&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616765%26dopt%3DAbstract Authors: Tükel C, Wilson RP, Nishimori JH, Pezeshki M, Chromy BA, Bäumler AJ Curli fibrils are proteinaceous bacterial structures formed by amyloid fibrils composed of the major curli subunit CsgA. Like beta-amyloid 1-42, which is associated with brain inflammation and Alzheimer's disease, curli fibrils have been implicated in the induction of host inflammatory responses. However, the underlying mechanisms of amyloid-induced inflammation are not fully understood. In a mouse sepsis model, we show that curli fibrils contributed to Nos2 expression, a hallmark of inflammation, by stimulating Toll-like receptor (TLR) 2. The TLR2 agonist activity was reduced by an amyloidogenicity-lowering amino acid substitution (N122A) in CsgA. Amyloid-forming synthetic peptides corresponding to ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627484 Wed, 22 Jul 2009 23:00:00 +0100 2627484 http://www.medworm.com/index.php?rid=2627480&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616766%26dopt%3DAbstract Authors: Kaushik R, Zhu X, Stranska R, Wu Y, Stevenson M Primate lentiviruses, including HIV-1, transduce terminally differentiated, nondividing myeloid cells; however, these cells are refractory to infection by gammaretroviruses such as murine leukemia virus (MLV). Here, we present evidence that a cellular restriction is the obstacle to transduction of macrophages by MLV. Neutralization of the restriction by Vpx, a primate lentiviral protein previously shown to protect primate lentiviruses from a macrophage restriction, rendered macrophages permissive to MLV infection. We further demonstrate that this restriction prevents transduction of quiescent monocytes by HIV-1. Monocyte-HeLa heterokaryons were resistant to HIV-1 infection, while heterokaryons formed between monocytes and HeLa ce... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627480 Wed, 22 Jul 2009 23:00:00 +0100 2627480 http://www.medworm.com/index.php?rid=2627479&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616767%26dopt%3DAbstract Authors: Chlanda P, Carbajal MA, Cyrklaff M, Griffiths G, Krijnse-Locker J The biogenesis and dynamics of cellular membranes are governed by fusion and fission processes that ensure the maintenance of closed compartments. These principles also apply to viruses during acquisition of their envelope. Based on conventional electron microscopy (EM), however, it has been proposed that poxviruses assemble from membranes made de novo with "free" ends in the cytoplasm. Here, we analyze the origin and structure of poxvirus membranes in a close-to-native state and in three dimensions by using cryopreservation and electron tomography (ET). By cryo-EM, the precursor membrane of poxviruses appears as an open membrane sheet stabilized by a protein scaffold. ET shows that this membrane is derived from... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627479 Wed, 22 Jul 2009 23:00:00 +0100 2627479 http://www.medworm.com/index.php?rid=2627478&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19616768%26dopt%3DAbstract Authors: Kallewaard NL, Zhang L, Chen JW, Guttenberg M, Sanchez MD, Bergelson JM In cultured cells, infection by group B coxsackievirus (CVB) is mediated by the coxsackievirus and adenovirus receptor (CAR), but the importance of this molecule in CVB-induced disease has not been determined. We generated mice with tissue-specific ablation of CAR within each of two major CVB target organs, the pancreas and heart. In the pancreas, deletion of CAR resulted in a significant reduction in both virus titers and virus-induced tissue damage. Similarly, cardiomyocyte-specific CAR deletion resulted in a marked reduction in virus titer, infection-associated cytokine production, and histopathology within the heart. Consistent with the in vivo phenotype, CAR-deficient cardiomyocytes resisted infection... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2627478 Wed, 22 Jul 2009 23:00:00 +0100 2627478 http://www.medworm.com/index.php?rid=2549229&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527877%26dopt%3DAbstract Authors: Mostowy S, Cossart P The study of how microbes cause disease has initiated unique research avenues in both infection biology and cell biology. As our knowledge of the infected cell improves and innovative technologies become available, new domains of investigation hold promise for better understanding pathogenesis and fundamental cellular processes. PMID: 19527877 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549229 Wed, 17 Jun 2009 23:00:00 +0100 2549229 http://www.medworm.com/index.php?rid=2549228&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527878%26dopt%3DAbstract Authors: Tegtmeyer N, Backert S Many pathogenic bacteria are able to surmount exfoliation and colonize the host epithelium efficiently. In a recent article in Nature, Kim et al. (2009) show that Shigella flexneri OspE, a conserved type III effector, reinforces host cell adherence and prevents detachment of the infected cells by interacting with integrin-linked kinase. PMID: 19527878 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549228 Wed, 17 Jun 2009 23:00:00 +0100 2549228 http://www.medworm.com/index.php?rid=2549227&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527879%26dopt%3DAbstract Authors: Bergelson JM Most viruses infect their hosts by crossing the mucosal surfaces of the respiratory, gastrointestinal, or genital tracts, then spread--often through the bloodstream--to other organs; they are shed in bodily secretions to reach new hosts. At each stage in the cycle of infection viruses surmount significant anatomic barriers. This Minireview focuses on the role of intercellular junctions as barriers to virus dissemination, and the somewhat paradoxical observation that several viruses, rather than evading these barriers, target them directly by using junctional proteins as receptors. PMID: 19527879 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549227 Wed, 17 Jun 2009 23:00:00 +0100 2549227 http://www.medworm.com/index.php?rid=2549226&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527880%26dopt%3DAbstract Authors: Comstock LE Much of the mutualistic relationship between humans and their resident intestinal Bacteroides species is founded on glycans. The host provides plant polysaccharides and host-derived glycans and, in return, receives beneficial end products of bacterial fermentation. Glycans from the bacteria themselves are required for the establishment and survival of these organisms in the colonic ecosystem and provide immunomodulatory properties to the host. Coordinated synthesis and catabolism of bacterial glycans is likely to contribute to the host-bacterial mutualism. PMID: 19527880 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549226 Wed, 17 Jun 2009 23:00:00 +0100 2549226 http://www.medworm.com/index.php?rid=2549225&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527881%26dopt%3DAbstract Authors: Deretic V, Levine B Autophagy adjusts cellular biomass and function in response to diverse stimuli, including infection. Autophagy plays specific roles in shaping immune system development, fueling host innate and adaptive immune responses, and directly controlling intracellular microbes as a cell-autonomous innate defense. As an evolutionary counterpoint, intracellular pathogens have evolved to block autophagic microbicidal defense and subvert host autophagic responses for their survival or growth. The ability of eukaryotic pathogens to deploy their own autophagic machinery may also contribute to microbial pathogenesis. Thus, a complex interplay between autophagy and microbial adaptations against autophagy governs the net outcome of host-microbe encounters. PMID: 19527881... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549225 Wed, 17 Jun 2009 23:00:00 +0100 2549225 http://www.medworm.com/index.php?rid=2549224&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527882%26dopt%3DAbstract Authors: Bieniasz PD Recent work has illuminated three critical aspects of the cell biology of HIV-1 particle genesis. First, we have come to understand which cellular membranes are selected as platforms for virus particle assembly and how this occurs. Second, an understanding of how the host ESCRT pathway enables virion budding is accruing. Third, it has become apparent that a host inhibitor can block HIV-1 particle release and that antagonism of this inhibitor underlies the ability of HIV and SIV accessory genes to facilitate particle release. Here, I review recent progress in these three areas. PMID: 19527882 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549224 Wed, 17 Jun 2009 23:00:00 +0100 2549224 http://www.medworm.com/index.php?rid=2549223&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527883%26dopt%3DAbstract Authors: Isaacson MK, Ploegh HL Ubiquitin is important for nearly every aspect of cellular physiology. All viruses rely extensively on host machinery for replication; therefore, it is not surprising that viruses connect to the ubiquitin pathway at many levels. Viral involvement with ubiquitin occurs either adventitiously because of the unavoidable usurpation of cellular processes, or for some specific purpose selected for by the virus to enhance viral replication. Here, we review current knowledge of how the ubiquitin pathway alters viral replication and how viruses influence the ubiquitin pathway to enhance their own replication. PMID: 19527883 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549223 Wed, 17 Jun 2009 23:00:00 +0100 2549223 http://www.medworm.com/index.php?rid=2549222&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527884%26dopt%3DAbstract Authors: Galán JE Central to the biology of many pathogenic bacteria are a number of specialized machines, known as type III, type IV, or type VI protein secretion systems. These machines have specifically evolved to deliver bacterial effector proteins into host cells with the capacity to modulate a variety of cellular functions. The identification of the biochemical activities of many effector proteins, coupled with a better understanding of their potential contribution to pathogenesis, has revealed common themes in the evolutionary design and function of these remarkable bacterial proteins. PMID: 19527884 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549222 Wed, 17 Jun 2009 23:00:00 +0100 2549222 http://www.medworm.com/index.php?rid=2549221&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527885%26dopt%3DAbstract Authors: Kline KA, Fälker S, Dahlberg S, Normark S, Henriques-Normark B Most commensal and pathogenic bacteria interacting with eukaryotic hosts express adhesive molecules on their surfaces that promote interaction with host cell receptors or with soluble macromolecules. Even though bacterial attachment to epithelial cells may be beneficial for bacterial colonization, adhesion may come at a cost because bacterial attachment to immune cells can facilitate phagocytosis and clearing. Many pathogenic bacteria have solved this dilemma by producing an antiphagocytic surface layer usually consisting of polysaccharide and by expressing their adhesins on polymeric structures that extend out from the cell surface. In this review, we will focus on the interaction between bacterial adhesins a... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549221 Wed, 17 Jun 2009 23:00:00 +0100 2549221 http://www.medworm.com/index.php?rid=2549220&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527886%26dopt%3DAbstract Authors: Kumar Y, Valdivia RH Many intracellular pathogens survive in vacuolar niches composed of host-derived membranes modified extensively by pathogen proteins and lipids. Although intracellular lifestyles offer protection from humoral immune responses, vacuole-bound pathogens nevertheless face powerful intracellular innate immune surveillance pathways that can trigger fusion with lysosomes, autophagy, and host cell death. Strategies used by vacuole-bound pathogens to invade and establish a replicative vacuole are well described, but how the integrity and stability of these parasitic vacuoles are maintained is poorly understood. Here, we identify potential mechanisms of pathogenic vacuole maintenance and the consequences of vacuole disruption by highlighting select bacterial and pro... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549220 Wed, 17 Jun 2009 23:00:00 +0100 2549220 http://www.medworm.com/index.php?rid=2549219&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527887%26dopt%3DAbstract Authors: Frénal K, Soldati-Favre D The phylum Apicomplexa includes a large and diverse group of obligate intracellular parasites that rely on actomyosin-based motility to migrate, enter host cells, and egress from infected cells. To ensure their intracellular survival and replication, the apicomplexans have evolved sophisticated strategies for subversion of the host cytoskeleton. Given the properties in common between the host and parasite cytoskeleton, dissecting their individual contribution to the establishment of parasitic infection has been challenging. Nevertheless, recent studies have provided new insights into the mechanisms by which parasites subvert the dynamic properties of host actin and tubulin to promote their entry, development, and egress. PMID: 19527887 [PubMe... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549219 Wed, 17 Jun 2009 23:00:00 +0100 2549219 http://www.medworm.com/index.php?rid=2549218&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19527888%26dopt%3DAbstract Authors: Billker O, Lourido S, Sibley LD Calcium controls many critical events in the complex life cycles of apicomplexan parasites including protein secretion, motility, and development. Calcium levels are normally tightly regulated and rapid release of calcium into the cytosol activates a family of calcium-dependent protein kinases (CDPKs), which are normally characteristic of plants. CDPKs present in apicomplexans have acquired a number of unique domain structures likely reflecting their diverse functions. Calcium regulation in parasites is closely linked to signaling by cyclic nucleotides and their associated kinases. This Review summarizes the pivotal roles that calcium- and cyclic nucleotide-dependent kinases play in unique aspects of parasite biology. PMID: 19527888 [PubMed ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2549218 Wed, 17 Jun 2009 23:00:00 +0100 2549218 http://www.medworm.com/index.php?rid=2473092&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19501037%26dopt%3DAbstract Authors: Zhang F, Wilson SJ, Landford WC, Virgen B, Gregory D, Johnson MC, Munch J, Kirchhoff F, Bieniasz PD, Hatziioannou T The tetherin/BST2/CD317 protein blocks the release of HIV-1 and other enveloped viruses by inducing tethering of nascent particles to infected cell surfaces. The HIV-1 Vpu protein antagonizes the antiviral activity of human but not monkey tetherins and many simian immunodeficiency viruses (SIVs) do not encode Vpu. Here, we show that the apparently "missing" antitetherin activity in SIVs has been acquired by several SIV Nef proteins. Specifically, SIV(MAC)/SIV(SMM), SIV(AGM), and SIV(BLU) Nef proteins can suppress tetherin activity. Notably, tetherin antagonism by SIV Nef proteins is species specific, is genetically separable from other Nef activities, and is most... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473092 Wed, 03 Jun 2009 04:00:00 +0100 2473092 http://www.medworm.com/index.php?rid=2473141&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454338%26dopt%3DAbstract Authors: MacMicking JD G.B. Shaw's entreaty, "Stimulate the phagocytes," found its perfect interlocutor in Carl Nathan. Nearly 40 years ago, Nathan discovered macrophages were activated via soluble mediators released from T-lymphocytes-later identified as interferon-gamma (IFN-gamma)-for killing microbial pathogens. This year's Robert Koch Prize celebrates a lasting legacy for innate immunity. PMID: 19454338 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473141 Fri, 08 May 2009 04:00:00 +0100 2473141 http://www.medworm.com/index.php?rid=2473139&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454339%26dopt%3DAbstract Authors: Walley NM, Julg B, Dickson SP, Fellay J, Ge D, Walker BD, Carrington M, Cohen MS, de Bakker PI, Goldstein DB, Shianna KV, Haynes BF, Letvin NL, McMichael AJ, Michael NL, Weintrob AC PMID: 19454339 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473139 Fri, 08 May 2009 04:00:00 +0100 2473139 http://www.medworm.com/index.php?rid=2473137&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454340%26dopt%3DAbstract Authors: Winkler CA, An P, Johnson R, Nelson GW, Kirk G PMID: 19454340 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473137 Fri, 08 May 2009 04:00:00 +0100 2473137 http://www.medworm.com/index.php?rid=2473135&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454341%26dopt%3DAbstract Authors: Julg B, Reddy S, van der Stok M, Kulkarni S, Qi Y, Bass S, Gold B, Nalls MA, Nelson GW, Walker BD, Carrington M, Ndung'u T PMID: 19454341 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473135 Fri, 08 May 2009 04:00:00 +0100 2473135 http://www.medworm.com/index.php?rid=2473133&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454342%26dopt%3DAbstract Authors: Horne KC, Li X, Jacobson LP, Palella F, Jamieson BD, Margolick JB, Martinson J, Turkozu V, Visvanathan K, Woolley IJ PMID: 19454342 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473133 Fri, 08 May 2009 04:00:00 +0100 2473133 http://www.medworm.com/index.php?rid=2473131&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454344%26dopt%3DAbstract Authors: Ludwig S, Wolff T The virulence of many pathogenic viruses depends on suppression of the innate type I interferon defense. For influenza viruses, a unique strategy has now been unraveled, as the viral nonstructural protein 1 was shown to inhibit activation of the pathogen recognition receptor RIG-I by binding the ubiquitin ligase TRIM25. PMID: 19454344 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473131 Fri, 08 May 2009 04:00:00 +0100 2473131 http://www.medworm.com/index.php?rid=2473129&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454345%26dopt%3DAbstract Authors: Skaar EP Nearly all bacterial pathogens require iron to successfully infect their vertebrate hosts. The host molecule lipocalin-2 exploits this by sequestering bacterial siderophores as a mechanism of protection against infection. Raffatellu et al. (2009) show that Salmonella enterica serotype Typhimurium circumvents this through the production of the modified siderophore salmochelin. PMID: 19454345 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473129 Fri, 08 May 2009 04:00:00 +0100 2473129 http://www.medworm.com/index.php?rid=2473127&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454346%26dopt%3DAbstract Authors: Zhang X, Zhang Y Communication between the nervous and immune systems is fundamental to animal physiology. However, the complicated anatomy and signaling pathways of these systems in mammals challenge the understanding of the neural-immune interaction at molecular, cellular, and organismic levels. Caenorhabditis elegans has been valuable in this regard because of its simple, well-defined nervous system and accessibility to genetic, molecular, and behavioral analyses. Recent studies in C. elegans have identified neuronal pathways that regulate signaling cascades in innate immune responses, including a neuroendocrine network, a TGF-beta pathway and dopaminergic neurotransmission, illuminating how specific neuronal signaling molecules and circuits control integrative immune respo... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473127 Fri, 08 May 2009 04:00:00 +0100 2473127 http://www.medworm.com/index.php?rid=2473125&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454347%26dopt%3DAbstract Authors: Sala C, Grainger DC, Cole ST Understanding host-microbe interactions has been greatly enhanced by our broadening knowledge of the regulatory mechanisms at the heart of pathogenesis. The "transcriptomics" approach of measuring global gene expression has identified genes involved in bacterial pathogenesis. More recently, chromatin immunoprecipitation (ChIP) and hybridization to microarrays (chIP-on-chip) has emerged as a complementary tool that permits protein-DNA interactions to be studied in vivo. Thus, chIP-on-chip can be used to map the binding sites of transcription factors, thereby teasing apart gene regulatory networks. In this Review, we discuss the ChIP-on-chip technique and focus on its application to the study of host-pathogen interactions. PMID: 19454347 [PubMed ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473125 Fri, 08 May 2009 04:00:00 +0100 2473125 http://www.medworm.com/index.php?rid=2473123&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454348%26dopt%3DAbstract Authors: Gack MU, Albrecht RA, Urano T, Inn KS, Huang IC, Carnero E, Farzan M, Inoue S, Jung JU, García-Sastre A The ubiquitin ligase TRIM25 mediates Lysine 63-linked ubiquitination of the N-terminal CARD domains of the viral RNA sensor RIG-I to facilitate type I interferon (IFN) production and antiviral immunity. Here, we report that the influenza A virus nonstructural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction. A novel domain in NS1 comprising E96/E97 residues mediates its interaction with the coiled-coil domain of TRIM25, thus blocking TRIM25 multimerization and RIG-I CARD domain ubiquitination. Furthermore, a recombinant influenza A virus expressing an E96A/E97A NS1 mutant is defective in block... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473123 Fri, 08 May 2009 04:00:00 +0100 2473123 http://www.medworm.com/index.php?rid=2473121&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454349%26dopt%3DAbstract Authors: Anyanful A, Easley KA, Benian GM, Kalman D Caenorhabditis elegans exhibits avoidance behavior when presented with diverse bacterial pathogens. We hypothesized that exposure to pathogens might not only cause worms to move away but also simultaneously activate pathways that promote resistance to the pathogen. We show that brief exposure to virulent or avirulent strains of the bacterial pathogen enteropathogenic E. coli (EPEC) "immunizes"C. elegans to survive a subsequent exposure that would otherwise prove lethal, a phenomenon we refer to as "conditioning." Conditioning requires dopaminergic neurons; the p38 MAP kinase pathway, which regulates innate immunity; and the insulin/IGFR pathway, which regulates lifespan. Our findings suggest that the molecular pathways that control in... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473121 Fri, 08 May 2009 04:00:00 +0100 2473121 http://www.medworm.com/index.php?rid=2473119&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454350%26dopt%3DAbstract Authors: Mysorekar IU, Isaacson-Schmid M, Walker JN, Mills JC, Hultgren SJ The transitional epithelium of the bladder normally turns over slowly but upon injury undergoes rapid regeneration fueled by basal uroepithelial stem and/or early progenitor cells (USCs). Little is known about the mechanisms underlying the injury response. We investigate the mechanism of bladder epithelial regeneration in response to infection with uropathogenic E. coli (UPEC). Infection resulted in rapid sloughing of superficial cells, a marked inflammatory response, and a substantial spike in basal cell proliferation. In mice with induced urothelial ablation of a member of the TGF-beta receptor superfamily, bone morphogenetic protein (Bmp)-4 receptor, infection led to aberrant urothelial renewal resulting from... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473119 Fri, 08 May 2009 04:00:00 +0100 2473119 http://www.medworm.com/index.php?rid=2473097&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454351%26dopt%3DAbstract Authors: Raffatellu M, George MD, Akiyama Y, Hornsby MJ, Nuccio SP, Paixao TA, Butler BP, Chu H, Santos RL, Berger T, Mak TW, Tsolis RM, Bevins CL, Solnick JV, Dandekar S, Bäumler AJ In response to enteric pathogens, the inflamed intestine produces antimicrobial proteins, a process mediated by the cytokines IL-17 and IL-22. Salmonella enterica serotype Typhimurium thrives in the inflamed intestinal environment, suggesting that the pathogen is resistant to antimicrobials it encounters in the intestinal lumen. However, the identity of these antimicrobials and corresponding bacterial resistance mechanisms remain unknown. Here, we report that enteric infection of rhesus macaques and mice with S. Typhimurium resulted in marked Il-17- and IL-22-dependent intestinal epithelial induction ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473097 Fri, 08 May 2009 04:00:00 +0100 2473097 http://www.medworm.com/index.php?rid=2473095&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454352%26dopt%3DAbstract Authors: Hise AG, Tomalka J, Ganesan S, Patel K, Hall BA, Brown GD, Fitzgerald KA Candida albicans is an opportunistic fungal pathogen causing life-threatening mucosal and systemic infections in immunocompromised humans. Using a murine model of mucosal Candida infection, we investigated the role of the proinflammatory cytokine IL-1beta in host defense to Candida albicans. We find that the synthesis, processing, and release of IL-1beta in response to Candida are tightly controlled and first require transcriptional induction, followed by a second signal leading to caspase-1-mediated cleavage of the pro-IL-1beta cytokine. The known fungal pattern recognition receptors TLR2 and Dectin-1 regulate IL-1beta gene transcription, whereas the NLRP3-containing proinflammatory multiprotein complex,... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473095 Fri, 08 May 2009 04:00:00 +0100 2473095 http://www.medworm.com/index.php?rid=2473093&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19454353%26dopt%3DAbstract Authors: Gupta L, Molina-Cruz A, Kumar S, Rodrigues J, Dixit R, Zamora RE, Barillas-Mury C The STAT family of transcription factors activates expression of immune system genes in vertebrates. The ancestral STAT gene (AgSTAT-A) appears to have duplicated in the mosquito Anopheles gambiae, giving rise to a second intronless STAT gene (AgSTAT-B), which we show regulates AgSTAT-A expression in adult females. AgSTAT-A participates in the transcriptional activation of nitric oxide synthase (NOS) in response to bacterial and plasmodial infection. Activation of this pathway, however, is not essential for mosquitoes to survive a bacterial challenge. AgSTAT-A silencing reduces the number of early Plasmodium oocysts in the midgut, but nevertheless enhances the overall infection by increasing oocy... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473093 Fri, 08 May 2009 04:00:00 +0100 2473093 http://www.medworm.com/index.php?rid=2473155&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380107%26dopt%3DAbstract Authors: Thomas M, Holden DW Ubiquitination has many important cellular functions, including regulation of plasma membrane endocytosis. In their recent article in Cell, Patel et al. (2009) show that the activity of the multifunctional Salmonella virulence protein SopB is controlled by ubiquitin-dependent delivery from the plasma membrane to the Salmonella-containing vacuole. PMID: 19380107 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473155 Thu, 23 Apr 2009 04:00:00 +0100 2473155 http://www.medworm.com/index.php?rid=2473154&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380108%26dopt%3DAbstract Authors: Levitz SM Th17 cells are thought to play a pivotal role in defenses against Candida albicans. van de Veerdonk et al. (2009) investigate components of the fungal cell wall and their cognate receptors on human peripheral blood mononuclear cells (PBMCs) responsible for IL-17 production and find a predominant role for mannan stimulation of the mannose receptor. PMID: 19380108 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473154 Thu, 23 Apr 2009 04:00:00 +0100 2473154 http://www.medworm.com/index.php?rid=2473153&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380109%26dopt%3DAbstract Authors: Coleman JJ, Mylonakis E Similarities in innate immune signaling exist between mammals and the nematode Caenorhabditis elegans. Now, Ziegler et al. (2009) and Ren et al. (2009) demonstrate that a protein kinase C delta homolog in C. elegans is involved in innate immunity, providing evidence that the conservation of immune signaling networks extends further than previously thought. PMID: 19380109 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473153 Thu, 23 Apr 2009 04:00:00 +0100 2473153 http://www.medworm.com/index.php?rid=2473152&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380110%26dopt%3DAbstract Authors: Dölken L, Jonjic S Herpesviruses subvert immune cell activation by inhibiting NK cell receptor (NKG2D)-activating ligands such as MICB. A human cytomegalovirus microRNA was recently shown to repress MICB expression. Nachmani et al. (2009) extend this finding to two other human herpesviruses, providing evidence for a conserved functional role of viral microRNAs despite no sequence conservation among them. PMID: 19380110 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473152 Thu, 23 Apr 2009 04:00:00 +0100 2473152 http://www.medworm.com/index.php?rid=2473151&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380111%26dopt%3DAbstract Authors: Fernandez-Garcia MD, Mazzon M, Jacobs M, Amara A Flaviviruses, such as the dengue virus and the West Nile virus, are emerging arthropod-borne viruses that represent an immense global health problem. Considerable progress has been made in understanding flavivirus structure and replication strategies, but only now are the complex molecular interactions between the virus and host cell starting to be unraveled. In this Review, we discuss the ongoing efforts toward elucidating the molecular mechanisms that allow flaviviruses to manipulate host cell functions for successful infection. We draw attention to the importance of these studies in defining the pathogenesis of flaviviral diseases. PMID: 19380111 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473151 Thu, 23 Apr 2009 04:00:00 +0100 2473151 http://www.medworm.com/index.php?rid=2473150&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380112%26dopt%3DAbstract This study identifies the specific pattern recognition receptors that trigger the Th17 response induced by a human pathogen in the absence of mitogenic stimulation. PMID: 19380112 [PubMed - indexed for MEDLINE] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473150 Thu, 23 Apr 2009 04:00:00 +0100 2473150 http://www.medworm.com/index.php?rid=2473149&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380113%26dopt%3DAbstract Authors: Ziegler K, Kurz CL, Cypowyj S, Couillault C, Pophillat M, Pujol N, Ewbank JJ Like other multicellular organisms, the model nematode C. elegans responds to infection by inducing the expression of defense genes. Among the genes upregulated in response to a natural fungal pathogen is nlp-29, encoding an antimicrobial peptide. In a screen for mutants that fail to express nlp-29 following fungal infection, we isolated alleles of tpa-1, homologous to the mammalian protein kinase C (PKC) delta. Through epistasis analyses, we demonstrate that C. elegans PKC acts through the p38 MAPK pathway to regulate nlp-29. This involves G protein signaling and specific C-type phospholipases acting upstream of PKCdelta. Unexpectedly and unlike in mammals, tpa-1 does not act via D-type protein kinas... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473149 Thu, 23 Apr 2009 04:00:00 +0100 2473149 http://www.medworm.com/index.php?rid=2473148&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380114%26dopt%3DAbstract Authors: Starnes GL, Coincon M, Sygusch J, Sibley LD Apicomplexan parasites rely on actin-based motility to drive host cell invasion. Prior in vitro studies implicated aldolase, a tetrameric glycolytic enzyme, in coupling actin filaments to the parasite's surface adhesin microneme protein 2 (MIC2). Here, we test the essentiality of this interaction in host cell invasion. Based on in vitro studies and homology modeling, we generated a series of mutations in Toxoplasma gondii aldolase (TgALD1) that delineated MIC2 tail domain (MIC2t) binding function from its enzyme activity. We tested these mutants by complementing a conditional knockout of TgALD1. Mutations that affected glycolysis also reduced motility. Mutants only affecting binding to MIC2t had no motility phenotype, but were decrea... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473148 Thu, 23 Apr 2009 04:00:00 +0100 2473148 http://www.medworm.com/index.php?rid=2473147&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380115%26dopt%3DAbstract Authors: Welsch S, Miller S, Romero-Brey I, Merz A, Bleck CK, Walther P, Fuller SD, Antony C, Krijnse-Locker J, Bartenschlager R Positive-strand RNA viruses are known to rearrange cellular membranes to facilitate viral genome replication. The biogenesis and three-dimensional organization of these membranes and the link between replication and virus assembly sites is not fully clear. Using electron microscopy, we find Dengue virus (DENV)-induced vesicles, convoluted membranes, and virus particles to be endoplasmic reticulum (ER)-derived, and we detect double-stranded RNA, a presumed marker of RNA replication, inside virus-induced vesicles. Electron tomography (ET) shows DENV-induced membrane structures to be part of one ER-derived network. Furthermore, ET reveals vesicle pores that coul... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473147 Thu, 23 Apr 2009 04:00:00 +0100 2473147 http://www.medworm.com/index.php?rid=2473146&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380116%26dopt%3DAbstract Authors: Nachmani D, Stern-Ginossar N, Sarid R, Mandelboim O Herpesviruses are known for their persistent lifelong latent infection, which is made possible by their vast repertoire of immune-evasion strategies. We have previously shown that a human cytomegalovirus (HCMV) microRNA represses expression of the stress-induced Natural Killer (NK) cell ligand, MICB, to escape recognition and consequent elimination by NK cells. Here, we show functional conservation among diverse microRNAs derived from different herpesviruses, including HCMV, Kaposi's sarcoma-associated herpesvirus (KSHV), and Epstein-Barr virus (EBV), in their ability to directly target MICB mRNA and reduce its expression. Although the various viral microRNAs share no sequence homology, they are functionally similar and targe... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473146 Thu, 23 Apr 2009 04:00:00 +0100 2473146 http://www.medworm.com/index.php?rid=2473145&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380117%26dopt%3DAbstract We describe here an efficient method for conditional gene inactivation in malaria parasites that uses the Flp/FRT site-specific recombination system of yeast. The method, developed in Plasmodium berghei, consists of inserting FRT sites in the chromosomal locus of interest in a parasite clone expressing the Flp recombinase via a developmental stage-specific promoter. Using promoters active in mosquito midgut sporozoites or salivary gland sporozoites to drive expression of Flp or its thermolabile variant, FlpL, we show that excision of the DNA flanked by FRT sites occurs efficiently at the stage of interest and at undetectable levels in prior stages. We applied this technique to conditionally silence MSP1, a gene essential for merozoite invasion of erythrocytes. Silencing MSP1 in sporozoites... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473145 Thu, 23 Apr 2009 04:00:00 +0100 2473145 http://www.medworm.com/index.php?rid=2473143&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19380118%26dopt%3DAbstract Authors: Selbach M, Paul FE, Brandt S, Guye P, Daumke O, Backert S, Dehio C, Mann M Selective interactions between tyrosine-phosphorylated proteins and their cognate, SH2-domain containing ligands play key roles in mammalian signal transduction. Several bacterial pathogens use secretion systems to inject tyrosine kinase substrates into host cells. Upon phosphorylation, these effector proteins recruit cellular binding partners to manipulate host cell functions. So far, only a few interaction partners have been identified. Here we report the results of a proteomic screen to systematically identify binding partners of all known tyrosine-phosphorylated bacterial effectors by high-resolution mass spectrometry. We identified 39 host interactions, all mediated by SH2 domains, including four o... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2473143 Thu, 23 Apr 2009 04:00:00 +0100 2473143 http://www.medworm.com/index.php?rid=2284194&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286134%26dopt%3DAbstract Authors: Weiss SM, Ladwein M, Schmidt D, Ehinger J, Lommel S, Städing K, Beutling U, Disanza A, Frank R, Jänsch L, Scita G, Gunzer F, Rottner K, Stradal TE Actin pedestal formation by pathogenic E. coli requires signaling by the bacterial intimin receptor Tir, which induces host cell actin polymerization mediated by N-WASP and the Arp2/3 complex. Whereas canonical enteropathogenic E. coli (EPEC) recruit these actin regulators through tyrosine kinase signaling cascades, enterohemorrhagic E. coli (EHEC) O157:H7 employ the bacterial effector EspF(U) (TccP), a potent N-WASP activator. Here, we show that IRSp53 family members, key regulators of membrane and actin dynamics, directly interact with both Tir and EspF(U). IRSp53 colocalizes with EspF(U) and N-WASP in actin pedestals. I... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2284194 Thu, 19 Mar 2009 04:00:00 +0100 2284194 http://www.medworm.com/index.php?rid=2274292&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286128%26dopt%3DAbstract Authors: Satchell KJ To colonize during disease and prevent consumption by environmental unicellular eukaryotes, bacteria often disrupt phagocytosis. In this issue, Ma et al. (2009) show that Vibrio cholerae delivers the actin-crosslinking T6SS effector VgrG-1 following phagocytosis. The effector then causes irreversible cytoskeleton destruction, leading to bystander protection of the extracellular bacterial population. PMID: 19286128 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274292 Wed, 18 Mar 2009 19:50:23 +0100 2274292 http://www.medworm.com/index.php?rid=2274287&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286129%26dopt%3DAbstract Authors: Yi CR, Goldberg MB Many pathogenic bacteria exploit host cytoskeletal pathways to promote infection. In this issue of Cell Host & Microbe, Weiss et al. (2009) identify the host factor IRSp53 as the missing link that connects two intracellular bacterial proteins, thereby completing an actin cytoskeletal signaling pathway critical to enterohemorrhagic Escherichia coli pathogenesis. PMID: 19286129 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274287 Wed, 18 Mar 2009 19:49:12 +0100 2274287 http://www.medworm.com/index.php?rid=2274283&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286130%26dopt%3DAbstract Authors: Collins KL Successful viruses must overcome the body's immune defenses. In this issue of Cell Host & Microbe, Goffinet et al. (2009) provide evidence that the host protein CD317, the target of the HIV Vpu protein, is part of an ancient innate immune response directed against budding viruses. PMID: 19286130 [PubMed - in process] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274283 Wed, 18 Mar 2009 19:47:40 +0100 2274283 http://www.medworm.com/index.php?rid=2274278&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286131%26dopt%3DAbstract Authors: Nathan C Despite scientific advances, we are losing ground against Mycobacterium tuberculosis, a pathogen with which a third of us share our lives. Challenges include fundamental biologic questions; hurdles for translational medicine; and societal deficits in resources, incentives, collaboration, and leadership. Fortunately, the crisis is inspiring scientific and organizational creativity. PMID: 19286131 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274278 Wed, 18 Mar 2009 19:46:51 +0100 2274278 http://www.medworm.com/index.php?rid=2274272&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286132%26dopt%3DAbstract Authors: Humphreys D, Hume PJ, Koronakis V Virulence effectors delivered into intestinal epithelial cells by Salmonella trigger actin remodeling to direct pathogen internalization and intracellular replication in Salmonella-containing vacuoles (SCVs). One such effector, SptP, functions early during pathogen entry to deactivate Rho GTPases and reverse pathogen-induced cytoskeletal changes following uptake. SptP also harbors a C-terminal protein tyrosine phosphatase (PTPase) domain with no clear host substrates. Investigating SptP's longevity in infected cells, we uncover a late function of SptP, showing that it associates with SCVs, and its PTPase activity increases pathogen replication. Direct SptP binding and specific dephosphorylation of the AAA+ ATPase valosin-containing protein (VC... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274272 Wed, 18 Mar 2009 19:46:03 +0100 2274272 http://www.medworm.com/index.php?rid=2274266&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286133%26dopt%3DAbstract Authors: Ma AT, McAuley S, Pukatzki S, Mekalanos JJ The type VI secretion system (T6SS) is a virulence mechanism common to several Gram-negative pathogens. In Vibrio cholerae, VgrG-1 is required for T6SS-dependent secretion. VgrG-1 is also secreted by T6SS and displays a C-terminal actin crosslinking domain (ACD). Using a heterologous reporter enzyme in place of the ACD, we show that the effector and secretion functions of VgrG-1 are genetically dissociable with the ACD being dispensable for secretion but required for T6SS-dependent phenotypes. Furthermore, internalization of bacteria is required for ACD translocation into phagocytic target cells. Inhibiting bacterial uptake abolishes actin crosslinking, while improving intracellular survival enhances it. Otherwise resistant nonphagocy... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274266 Wed, 18 Mar 2009 19:45:06 +0100 2274266 http://www.medworm.com/index.php?rid=2274261&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286134%26dopt%3DAbstract Authors: Weiss SM, Ladwein M, Schmidt D, Ehinger J, Lommel S, Städing K, Beutling U, Disanza A, Frank R, Jänsch L, Scita G, Gunzer F, Rottner K, Stradal TE Actin pedestal formation by pathogenic E. coli requires signaling by the bacterial intimin receptor Tir, which induces host cell actin polymerization mediated by N-WASP and the Arp2/3 complex. Whereas canonical enteropathogenic E. coli (EPEC) recruit these actin regulators through tyrosine kinase signaling cascades, enterohemorrhagic E. coli (EHEC) O157:H7 employ the bacterial effector EspF(U) (TccP), a potent N-WASP activator. Here, we show that IRSp53 family members, key regulators of membrane and actin dynamics, directly interact with both Tir and EspF(U). IRSp53 colocalizes with EspF(U) and N-WASP in actin pedestals. I... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274261 Wed, 18 Mar 2009 19:44:08 +0100 2274261 http://www.medworm.com/index.php?rid=2274253&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286135%26dopt%3DAbstract Authors: Gonzalez V, Combe A, David V, Malmquist NA, Delorme V, Leroy C, Blazquez S, Ménard R, Tardieux I Apicomplexa are obligate intracellular parasites that actively invade host cells using their membrane-associated, actin-myosin motor. The current view is that host cell invasion by Apicomplexa requires the formation of a parasite-host cell junction, which has been termed the moving junction, but does not require the active participation of host actin. Using Toxoplasma gondii tachyzoites and Plasmodium berghei sporozoites, we show that host actin participates in parasite entry. Parasites induce the formation of a ring-shaped F-actin structure in the host cell at the parasite-cell junction, which remains stable during parasite entry. The Arp2/3 complex, an actin-nucleating facto... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274253 Wed, 18 Mar 2009 19:43:30 +0100 2274253 http://www.medworm.com/index.php?rid=2274247&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286136%26dopt%3DAbstract Authors: Fraiture M, Baxter RH, Steinert S, Chelliah Y, Frolet C, Quispe-Tintaya W, Hoffmann JA, Blandin SA, Levashina EA Plasmodium development within Anopheles mosquitoes is a vulnerable step in the parasite transmission cycle, and targeting this step represents a promising strategy for malaria control. The thioester-containing complement-like protein TEP1 and two leucine-rich repeat (LRR) proteins, LRIM1 and APL1, have been identified as major mosquito factors that regulate parasite loads. Here, we show that LRIM1 and APL1 are required for binding of TEP1 to parasites. RNAi silencing of the LRR-encoding genes results in deposition of TEP1 on Anopheles tissues, thereby depleting TEP1 from circulation in the hemolymph and impeding its binding to Plasmodium. LRIM1 and APL1 not only sta... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274247 Wed, 18 Mar 2009 19:42:46 +0100 2274247 http://www.medworm.com/index.php?rid=2274242&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286137%26dopt%3DAbstract Authors: Goffinet C, Allespach I, Homann S, Tervo HM, Habermann A, Rupp D, Oberbremer L, Kern C, Tibroni N, Welsch S, Krijnse-Locker J, Banting G, Kräusslich HG, Fackler OT, Keppler OT Mammals encode proteins that inhibit viral replication at the cellular level. In turn, certain viruses have evolved genes that can functionally counteract these intrinsic restrictions. Human CD317 (BST-2/HM1.24/tetherin) is a restriction factor that blocks release of human immunodeficiency virus type 1 (HIV-1) from the cell surface and can be overcome by HIV-1 Vpu. Here, we show that mouse and rat CD317 potently inhibit HIV-1 release but are resistant to Vpu. Interspecies chimeras reveal that the rodent-specific resistance and human-specific sensitivity to Vpu antagonism involve all three major stru... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274242 Wed, 18 Mar 2009 19:41:38 +0100 2274242 http://www.medworm.com/index.php?rid=2274237&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19286138%26dopt%3DAbstract Authors: Tai AW, Benita Y, Peng LF, Kim SS, Sakamoto N, Xavier RJ, Chung RT Hepatitis C virus (HCV) chronically infects 3% of the world's population, and complications from HCV are the leading indication for liver transplantation. Given the need for better anti-HCV therapies, one strategy is to identify and target cellular cofactors of the virus lifecycle. Using a genome-wide siRNA library, we identified 96 human genes that support HCV replication, with a significant number of them being involved in vesicle organization and biogenesis. Phosphatidylinositol 4-kinase PI4KA and multiple subunits of the COPI vesicle coat complex were among the genes identified. Consistent with this, pharmacologic inhibitors of COPI and PI4KA blocked HCV replication. Targeting hepcidin, a peptide critical f... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2274237 Wed, 18 Mar 2009 19:40:00 +0100 2274237 http://www.medworm.com/index.php?rid=2192028&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19218080%26dopt%3DAbstract Authors: Galluzzi L, Kroemer G In nonmyeloid cells, Shigella hijacks the mitochondrial checkpoint of cell death, thereby inducing a regulated form of necrosis depending on Bnip3 and cyclophilin D. Carneiro et al. (2009) describe the interplay between this program and a prosurvival response transmitted via the Nod1/Rip2/NF-kappaB/Bcl-2 axis, which determines the fate of infected cells. PMID: 19218080 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2192028 Wed, 18 Feb 2009 02:22:25 +0100 2192028 http://www.medworm.com/index.php?rid=2192027&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19218081%26dopt%3DAbstract Authors: Boneca IG Peptidoglycan-recognition proteins (PGRPs) play a central role in the insect innate immune response to bacteria. In this issue of Cell Host & Microbe, Saha et al. (2009) report that the mammalian PGRP, PGLYRP-2, functions as a cytokine-like molecule in a PG-induced arthritis model. PMID: 19218081 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2192027 Wed, 18 Feb 2009 02:22:19 +0100 2192027 http://www.medworm.com/index.php?rid=2192026&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19218082%26dopt%3DAbstract Authors: Deitsch KW Gene families in malaria parasites that encode hypervariable surface antigens display mutually exclusive expression that is controlled epigenetically. In this issue, Lopez-Rubio et al. (2009) show that the histone mark H3K9me3 is specifically associated with regulation of expression of these gene families within repressive centers located at the nuclear periphery. PMID: 19218082 [PubMed - as supplied by publisher] (Source: Cell Host and Microbe) Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2192026 Wed, 18 Feb 2009 02:22:07 +0100 2192026 http://www.medworm.com/index.php?rid=2192025&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19218083%26dopt%3DAbstract Authors: Lebeis SL, Kalman D Drug-resistant microorganisms pose an enormous threat to public health. Here we provide examples of experimental approaches that offer novel ways to think about drug development considering the complexity inherent to host-pathogen interactions. Emergent themes include (1) targeting pathogenicity rather than microbial growth, (2) targeting the host or host-pathogen interface rather than the pathogen, (3) facilitating pathogen-specific immune responses, and (4) utilizing systems-based approaches to identify new drug targets and validate drug efficacy. We posit that together these approaches may allow identification of drugs that disrupt pathogenesis and allow the immune system time to protect, but do not easily engender resistance. PMID: 19218083 [PubMed ... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2192025 Wed, 18 Feb 2009 02:21:55 +0100 2192025 http://www.medworm.com/index.php?rid=2192024&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19218084%26dopt%3DAbstract Authors: Carneiro LA, Travassos LH, Soares F, Tattoli I, Magalhaes JG, Bozza MT, Plotkowski MC, Sansonetti PJ, Molkentin JD, Philpott DJ, Girardin SE Shigella rapidly kills myeloid cells via a caspase-1 inflammasome-dependent cell death mechanism. However, despite a critical role for nonmyeloid cells in the physiopathology of Shigella infection, the mechanism by which Shigella kills nonmyeloid cells remains uncharacterized. Here we demonstrate that, in nonmyeloid cells, Shigella infection induces loss of mitochondrial inner membrane potential, mitochondrial damage, and necrotic cell death through a pathway dependent on Bnip3 and cyclophilin D, two molecules implicated in the host oxidative stress responses. This mitochondrial cell death mechanism was potently counterbalanced by a Nod1-... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2192024 Wed, 18 Feb 2009 02:21:40 +0100 2192024 http://www.medworm.com/index.php?rid=2192023&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19218085%26dopt%3DAbstract Authors: Saha S, Qi J, Wang S, Wang M, Li X, Kim YG, Núñez G, Gupta D, Dziarski R Peptidoglycan recognition proteins (PGRPs) are structurally conserved from insects to mammals. Insect PGRPs have diverse host-defense functions. Mammalian PGRPs PGLYRP-1, PGLYRP-3, and PGLYRP-4 have bactericidal activity, while PGLYRP-2 has amidase activity. To extend the known functions of mammalian PGRPs, we examined whether they have immunomodulating activities in peptidoglycan-induced arthritis in mice. We demonstrate that PGLYRP-2 and Nod2 are both required for arthritis in this model. The sequence of events in peptidoglycan-induced arthritis is activation of Nod2, local expression of PGLYRP-2, chemokine production, and recruitment of neutrophils into the limbs, which induces acute arthriti... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2192023 Wed, 18 Feb 2009 02:21:30 +0100 2192023 http://www.medworm.com/index.php?rid=2192022&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19218086%26dopt%3DAbstract Authors: Xia Y, Gao QM, Yu K, Lapchyk L, Navarre D, Hildebrand D, Kachroo A, Kachroo P Systemic acquired resistance (SAR), initiated by a plant upon recognition of microbial effectors, involves generation of a mobile signal at the primary infection site, which translocates to and activates defense responses in distal tissues via unknown mechanism(s). We find that an acyl carrier protein, ACP4, is required to perceive the mobile SAR signal in distal tissues of Arabidopsis. Although acp4 plants generated the mobile signal, they failed to induce the systemic immunity response. Defective SAR in acp4 plants was not due to impairment in salicylic acid (SA)-, methyl SA-, or jasmonic acid-mediated plant hormone signaling pathways but was associated with the impaired cuticle of acp4 leaves. Oth... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2192022 Wed, 18 Feb 2009 02:21:15 +0100 2192022 http://www.medworm.com/index.php?rid=2192021&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19218087%26dopt%3DAbstract Authors: Hwang S, Kim KS, Flano E, Wu TT, Tong LM, Park AN, Song MJ, Sanchez DJ, O'Connell RM, Cheng G, Sun R A conserved herpesviral kinase, designated ORF36 in murine gamma-herpesvirus 68 (MHV-68), plays multiple vital roles in the viral life cycle. Here, we show by screening mutant viruses that ORF36 counteracts the antiviral type I interferon (IFN) response. ORF36 specifically binds to the activated form of interferon regulatory factor 3 (IRF-3) in the nucleus, inhibiting IRF-3 interaction with the cotranscriptional activator CBP and thereby suppressing the recruitment of RNA polymerase II to the interferon beta promoter. The anti-IFN function of ORF36 is conserved among herpesvirus subfamilies, although the conserved kinase activity is not absolutely required for this function. MH... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2192021 Wed, 18 Feb 2009 02:21:05 +0100 2192021 http://www.medworm.com/index.php?rid=2192020&cid=s_37761_77_f&fid=37761&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19218088%26dopt%3DAbstract Authors: Lopez-Rubio JJ, Mancio-Silva L, Scherf A Clonally variant gene families underlie phenotypic plasticity in Plasmodium falciparum, a process indispensable for survival of the pathogen in its human host. Differential transcription of one of these gene families in clonal parasite lineages has been associated with chromatin modifications. Here, we determine the genome-wide distribution in P. falciparum of a histone mark of heterochromatin, trimethylation of histone H3 lysine 9 (H3K9me3), using high-resolution ChIP-chip analysis. We show that H3K9me3 is specifically associated with clonally variant gene families, which are clustered on subtelomeric and some chromosome internal regions. High levels of H3K9me3 correlate with genes localized to the nuclear periphery, implying chromosom... Cell Host and Microbe journals http://www.medworm.com/rss/comments.php?id=2192020 Wed, 18 Feb 2009 02:20:50 +0100 2192020