Regulation of macrophage cell surface GAPDH alters LL-37 internalization and downstream effects in the cell
Mycobacterium tuberculosis (M.tb), the major causative agent of tuberculosis (TB), has evolved mechanisms to evade host defenses and persist within host cells. Host directed therapies (HDTs) against infected cells are emerging as an effective option. Cationic host defense peptide LL-37 is known to internalize into cells and induce autophagy resulting in intracellular killing of M.tb. This peptide also regulates the immune system and interacts with the multifunctional protein Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), inside macrophages. Our investigations revealed that GAPDH moonlights as a mononuclear cell surface ...
Source: Journal of Innate Immunity - April 20, 2023 Category: Allergy & Immunology Source Type: research
Formyl peptide receptor type 2 (FPR2) deficiency in myeloid cells amplifies sepsis-induced cardiac dysfunction
In conclusion, FPR2 deficiency in myeloid cells exacerbates cardiac dysfunction and worsens clinical outcome in polymicrobial sepsis. The improvement of cardiac function and the host immune response by AnxA1 is more effective in hFPR2 competent septic mice. (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - April 17, 2023 Category: Allergy & Immunology Source Type: research
TLR7 activation in M-CSF-dependent monocyte-derived human macrophages potentiates inflammatory responses and prompts neutrophil recruitment
We present evidences that TLR7 is preferentially expressed by monocyte-derived macrophages generated in the presence of M-CSF (M-M Ø). We now show that TLR7 activation in M-MØ triggers a weak MAPK, NFκB and STAT1 activation and results in low production of type I IFN. Of note, TLR7 engagement re-programs MAFB+ M-MØ towards a pro-inflammatory transcriptional profile characterized by the expression of neutrophil-attracting ch emokines (CXCL1-3, CXCL5, CXCL8), whose expression is dependent on the transcription factors MAFB and AhR. Moreover, TLR7-activated M-MØ display enhanced pro-inflammatory responses and a stronger p...
Source: Journal of Innate Immunity - April 11, 2023 Category: Allergy & Immunology Source Type: research
Interactions between Macrophages and Biofilm during < i > Staphylococcus aureus < /i > -Associated Implant Infection: Difficulties and Solutions
Staphylococcus aureus (S. aureus) biofilm is the major cause of failure of implant infection treatment that results in heavy social and economic burden on individuals, families, and communities. PlanktonicS. aureus attaches to medical implant surfaces where it proliferates and is wrapped by extracellular polymeric substances, forming a solid and complex biofilm. This provides a stable environment for bacterial growth, infection maintenance, and diffusion and protects the bacteria from antimicrobial agents and the immune system of the host. Macrophages are an important component of the innate immune system and resist pathog...
Source: Journal of Innate Immunity - April 3, 2023 Category: Allergy & Immunology Source Type: research
Interactions between macrophages and biofilm during Staphylococcus aureus-associated implant infection: difficulties and solutions
Staphylococcus aureus (S. aureus) biofilm is the major cause of failure of implant infection treatment that results in heavy social and economic burden on individuals, families, and communities. Planktonic S. aureus attaches to medical implant surfaces where it proliferates and is wrapped by extracellular polymeric substances (EPS), forming a solid and complex biofilm. This provides a stable environment for bacterial growth, infection maintenance, and diffusion, and protects the bacteria from antimicrobial agents and the immune system of the host. Macrophages are an important component of the innate immune system, and resi...
Source: Journal of Innate Immunity - April 3, 2023 Category: Allergy & Immunology Source Type: research
Single Cell Analysis of the Fate of Injected Oncogenic RasV12 Cells in Adult Wild Type < i > Drosophila < /i >
We have injected dish-cultured oncogenic RasV12 cells into adult male flies and analyzed by single cell transcriptomics their destiny within the host after 11 days. We identified in the preinjection samples and in the 11-day postinjection samples in all 16 clusters of cells, of which 5 disappeared during the experiment in the host. The other cell clusters expanded and expressed genes involved in the regulation of cell cycle, metabolism, and development. In addition, three clusters expressed genes related to inflammation and defense. Predominant among these were genes coding for phagocytosis and/or characteristic for plasma...
Source: Journal of Innate Immunity - March 30, 2023 Category: Allergy & Immunology Source Type: research
Impact of changes in human airway epithelial cellular composition and differentiation on SARS-CoV-2 infection biology
In conclusion, our study demonstrates that viral replication is affected by changes in cellular composition, especially in cells related to the mucociliary system. This could explain in part the variable susceptibility to SARS-CoV-2 infection between individuals and between anatomical locations in the respiratory tract. (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - March 25, 2023 Category: Allergy & Immunology Source Type: research
Degradation of Ubiquitin-Editing Enzyme A20 following Autophagy Activation Promotes RNF168 Nuclear Translocation and NF- κB Activation in Lupus Nephritis
This study aimed to evaluate the potential role of this regulatory interaction in the pathogenesis of lupus nephritis (LN). The expression of RNF168 and A20 was measured in the podocytes derived from MRL/lpr murine lupus as well as patients with LN. Cell-based studies using renal podocytes bearing silenced RNF168, over-expressed A20, autophagy-related gene (Atg) 5 (a ubiquitin-like modifier), or silenced Atg5 were used to assess the effect of RNF168, A20, and Atg5 on DNA damage repair and nuclear factor kappa-B (NF- κB) activation in LN. It was found that podocyte autophagy was over-activated in LN and the abnormal podocy...
Source: Journal of Innate Immunity - March 21, 2023 Category: Allergy & Immunology Source Type: research
Interleukin-33 Ameliorates Murine Systemic Lupus Erythematosus and Is Associated with Induction of M2 Macrophage Polarisation and Regulatory T Cells
This study sought to examine the effect of exogenous IL-33 on disease activity of pre-disease lupus-prone mice and the underlying cellular mechanisms. Recombinant IL-33 was administered to MRL/lpr mice for 6 weeks, whereas control group received phosphate-buffered saline. IL-33-treated mice displayed less proteinuria, renal histological inflammatory changes, and had lower serum levels of pro-inflammatory cytokines including IL-6 and TNF- α. Renal tissue and splenic CD11b+ extracts showed features of M2 polarisation with elevated mRNA expression of Arg1, FIZZI, and reduced iNOS. These mice also had increased IL-13, ST2, Ga...
Source: Journal of Innate Immunity - March 8, 2023 Category: Allergy & Immunology Source Type: research
