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A Tail of Tetherin: How Pandemic HIV-1 Conquered the World.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Gupta RK, Towers GJ Tags: Cell Host Microbe Source Type: journals

Jenner's Irony: Cowpox Taps into T Cell Evasion.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Wilkinson GW, Lehner PJ Tags: Cell Host Microbe Source Type: journals

How aging compromises antiviral defenses: a role for imbalanced innate cytokine production.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Guiton R, Dalod M Tags: Cell Host Microbe Source Type: journals

A bacterial pathogen flips the riboswitch.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Xayarath B, Freitag NE Tags: Cell Host Microbe Source Type: journals

War and Peace between Microbes: HIV-1 Interactions with Coinfecting Viruses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Lisco A, Vanpouille C, Margolis L Tags: Cell Host Microbe Source Type: journals

Tetherin-Driven Adaptation of Vpu and Nef Function and the Evolution of Pandemic and Nonpandemic HIV-1 Strains.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
rchhoff 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 significant barrier to zoonotic transmission of SIVcpz to humans. Remarkably, Vpus from nonpandemic HIV...
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology 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, K Tags: Cell Host Microbe Source Type: journals

Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8 T cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 an...
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Byun M, Verweij MC, Pickup DJ, Wiertz EJ, Hansen TH, Yokoyama WM Tags: Cell Host Microbe Source Type: journals

Cowpox virus inhibits the transporter associated with antigen processing to evade T cell recognition.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 translocati...
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Alzhanova D, Edwards DM, Hammarlund E, Scholz IG, Horst D, Wagner MJ, Upton C, Wiertz EJ, Slifka MK, Früh K Tags: Cell Host Microbe Source Type: journals

Aging Promotes Neutrophil-Induced Mortality by Augmenting IL-17 Production during Viral Infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 m...
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Stout-Delgado HW, Du W, Shirali AC, Booth CJ, Goldstein DR Tags: Cell Host Microbe Source Type: journals

Induced ER Chaperones Regulate a Receptor-like Kinase to Mediate Antiviral Innate Immune Response in Plants.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Caplan JL, Zhu X, Mamillapalli P, Marathe R, Anandalakshmi R, Dinesh-Kumar SP Tags: Cell Host Microbe Source Type: journals

Inflammatory Monocytes Facilitate Adaptive CD4 T Cell Responses during Respiratory Fungal Infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Hohl TM, Rivera A, Lipuma L, Gallegos A, Shi C, Mack M, Pamer EG Tags: Cell Host Microbe Source Type: journals

Antibodies against a Tick Protein, Salp15, Protect Mice from the Lyme Disease Agent.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 p...
Source: Cell Host and Microbe - November 18, 2009 Category: Microbiology Authors: Dai J, Wang P, Adusumilli S, Booth CJ, Narasimhan S, Anguita J, Fikrig E Tags: Cell Host Microbe Source Type: journals

Taming supplemental material.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19837365 [PubMed - in process] (Source: Cell Host and Microbe)
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Marcus E Tags: Cell Host Microbe Source Type: journals

Mining the B Cell Repertoire for Broadly Neutralizing Monoclonal Antibodies to HIV-1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Kwong PD, Mascola JR, Nabel GJ Tags: Cell Host Microbe Source Type: journals

Tuning Down NF-kappaB Signaling by DUBs: A Fly Case.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Leulier F Tags: Cell Host Microbe Source Type: journals

Eating Twice for the Sake of Immunity: A Phagocytic Receptor that Activates Autophagy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Shahnazari S, Brumell JH Tags: Cell Host Microbe Source Type: journals

Autophagy, apoptosis, and the influenza virus m2 protein.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Rossman JS, Lamb RA Tags: Cell Host Microbe Source Type: journals

Homeostasis in infected epithelia: stem cells take the lead.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Pitsouli C, Apidianakis Y, Perrimon N Tags: Cell Host Microbe Source Type: journals

The Drosophila Ubiquitin-Specific Protease dUSP36/Scny Targets IMD to Prevent Constitutive Immune Signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 Tol...
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Thevenon D, Engel E, Avet-Rochex A, Gottar M, Bergeret E, Tricoire H, Benaud C, Baudier J, Taillebourg E, Fauvarque MO Tags: Cell Host Microbe Source Type: journals

Tissue-Specific Activities of an Immune Signaling Module Regulate Physiological Responses to Pathogenic and Nutritional Bacteria in C. elegans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 aversi...
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Shivers RP, Kooistra T, Chu SW, Pagano DJ, Kim DH Tags: Cell Host Microbe Source Type: journals

Mast Cells Augment Adaptive Immunity by Orchestrating Dendritic Cell Trafficking through Infected Tissues.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 traffick...
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Shelburne CP, Nakano H, St John AL, Chan C, McLachlan JB, Gunn MD, Staats HF, Abraham SN Tags: Cell Host Microbe Source Type: journals

Divergence of macrophage phagocytic and antimicrobial programs in leprosy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 differential regu...
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology 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 Tags: Cell Host Microbe Source Type: journals

Autophagy Induction by the Pathogen Receptor CD46.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 p...
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Joubert PE, Meiffren G, Grégoire IP, Pontini G, Richetta C, Flacher M, Azocar O, Vidalain PO, Vidal M, Lotteau V, Codogno P, Rabourdin-Combe C, Faure M Tags: Cell Host Microbe Source Type: journals

Matrix protein 2 of influenza a virus blocks autophagosome fusion with lysosomes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 inhibition of aut...
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology 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 Tags: Cell Host Microbe Source Type: journals

Complement protein c1q reduces the stoichiometric threshold for antibody-mediated neutralization of west nile virus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Cell Host and Microbe - October 21, 2009 Category: Microbiology Authors: Mehlhop E, Nelson S, Jost CA, Gorlatov S, Johnson S, Fremont DH, Diamond MS, Pierson TC Tags: Cell Host Microbe Source Type: journals

Making sense of antisense in antibiotic drug discovery.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology Authors: Wright GD Tags: Cell Host Microbe Source Type: journals

Shifting the paradigm: host gene signatures for diagnosis of infectious diseases.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology Authors: Ramilo O, Mejías A Tags: Cell Host Microbe Source Type: journals

A vitamin for autophagy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology Authors: Fabri M, Modlin RL Tags: Cell Host Microbe Source Type: journals

Host Tolerance versus Resistance and Microbial Virulence in the Host-Pathogen Equation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology Authors: Ferrandon D Tags: Cell Host Microbe Source Type: journals

Massive Secretion by T Cells Is Caused by HIV Nef in Infected Cells and by Nef Transfer to Bystander Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 exo...
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology 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 Tags: Cell Host Microbe Source Type: journals

Vitamin D3 Induces Autophagy in Human Monocytes/Macrophages via Cathelicidin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mycobact...
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology Authors: Yuk JM, Shin DM, Lee HM, Yang CS, Jin HS, Kim KK, Lee ZW, Lee SH, Kim JM, Jo EK Tags: Cell Host Microbe Source Type: journals

p38 MAPK-Dependent Phagocytic Encapsulation Confers Infection Tolerance in Drosophila.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 w...
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology Authors: Shinzawa N, Nelson B, Aonuma H, Okado K, Fukumoto S, Miura M, Kanuka H Tags: Cell Host Microbe Source Type: journals

The Amoebal MAP Kinase Response to Legionella pneumophila Is Regulated by DupA.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 pa...
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology Authors: Li Z, Dugan AS, Bloomfield G, Skelton J, Ivens A, Losick V, Isberg RR Tags: Cell Host Microbe Source Type: journals

Regulatory Mimicry in Listeria monocytogenes Actin-Based Motility.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology Authors: Chong R, Swiss R, Briones G, Stone KL, Gulcicek EE, Agaisse H Tags: Cell Host Microbe Source Type: journals

Identifying genetic determinants needed to establish a human gut symbiont in its habitat.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Host and Microbe - September 16, 2009 Category: Microbiology Authors: Goodman AL, McNulty NP, Zhao Y, Leip D, Mitra RD, Lozupone CA, Knight R, Gordon JI Tags: Cell Host Microbe Source Type: journals

Fly Antiviral RNA Silencing and miRNA Biogenesis Claim ARS2.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Voinnet O Tags: Cell Host Microbe Source Type: journals

Bacterial jailbreak sounds cellular alarm: phagosome membrane remnants trigger signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Hilbi H Tags: Cell Host Microbe Source Type: journals

A Gut Feeling for Microbes: Getting It Going between a Parasite and Its Host.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Denkers EY Tags: Cell Host Microbe Source Type: journals

Insect immunity: from pattern recognition to symbiont-mediated host defense.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Welchman DP, Aksoy S, Jiggins F, Lemaitre B Tags: Cell Host Microbe Source Type: journals

Microbial telesensing: probing the environment for friends, foes, and food.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Roux A, Payne SM, Gilmore MS Tags: Cell Host Microbe Source Type: journals

The S. Typhimurium Effector SopE Induces Caspase-1 Activation in Stromal Cells to Initiate Gut Inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 mu...
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Müller AJ, Hoffmann C, Galle M, Van Den Broeke A, Heikenwalder M, Falter L, Misselwitz B, Kremer M, Beyaert R, Hardt WD Tags: Cell Host Microbe Source Type: journals

Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 m...
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Dupont N, Lacas-Gervais S, Bertout J, Paz I, Freche B, Van Nhieu GT, van der Goot FG, Sansonetti PJ, Lafont F Tags: Cell Host Microbe Source Type: journals

An Essential Role for RIG-I in Toll-like Receptor-Stimulated Phagocytosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 macrop...
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology 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 Tags: Cell Host Microbe Source Type: journals

Reduced Levels of Protein Tyrosine Phosphatase CD45 Protect Mice from the Lethal Effects of Ebola Virus Infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 ...
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Panchal RG, Bradfute SB, Peyser BD, Warfield KL, Ruthel G, Lane D, Kenny TA, Anderson AO, Raschke WC, Bavari S Tags: Cell Host Microbe Source Type: journals

HIV-1 Nef Interferes with Host Cell Motility by Deregulation of Cofilin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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...
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Stolp B, Reichman-Fried M, Abraham L, Pan X, Giese SI, Hannemann S, Goulimari P, Raz E, Grosse R, Fackler OT Tags: Cell Host Microbe Source Type: journals

Gut Commensal Bacteria Direct a Protective Immune Response against Toxoplasma gondii.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 impaire...
Source: Cell Host and Microbe - August 19, 2009 Category: Microbiology Authors: Benson A, Pifer R, Behrendt CL, Hooper LV, Yarovinsky F Tags: Cell Host Microbe Source Type: journals

Gene Expression Signatures Diagnose Influenza and Other Symptomatic Respiratory Viral Infections in Humans.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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 in an indepe...
Source: Cell Host and Microbe - August 4, 2009 Category: Microbiology 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 Tags: Cell Host Microbe Source Type: journals

CarD tricks and magic spots: mechanisms of stringent control in mycobacteria.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - July 22, 2009 Category: Microbiology Authors: Connolly LE, Cox JS Tags: Cell Host Microbe Source Type: journals

Finding Leishmania: a deadly game of hide-and-seek.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
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)
Source: Cell Host and Microbe - July 22, 2009 Category: Microbiology Authors: Scott P Tags: Cell Host Microbe Source Type: journals

Humanized mice for modeling human infectious disease: challenges, progress, and outlook.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
tevens 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 Microbe)
Source: Cell Host and Microbe - July 22, 2009 Category: Microbiology 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, Tags: Cell Host Microbe Source Type: journals