ArticleCell communication and signaling : CCS2016
Role of PKCtheta in macrophage-mediated immune response to Salmonella typhimurium infection in mice.
Article in Cell communication and signaling : CCS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Unlocking the power of swine gut bacteria: newly isolated Blautia strain and its metabolites inhibit the replication of Salmonella Typhimurium in macrophages and alleviate DSS-induced colitis in mice.Journal of animal science and biotechnology · 2025Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Diagnostic and prognostic value of autophagy-related key genes in sepsis and potential correlation with immune cell signatures.Frontiers in cell and developmental biology · 2023Article
- Bioinformatics analyses of potential ACLF biological mechanisms and identification of immune-related hub genes and vital miRNAs.Scientific reports · 2022Article
- Extracellular vesicle-mediated regulation of macrophage polarization in bacterial infections.Frontiers in microbiology · 2022Review
- Thrombospondin-1 aggravates colonic mucosal inflammatory injuries via promoting the differentiation of CD11cAnnals of translational medicine · 2021Article
- Short-term transcriptomic response to plasma membrane injury.Scientific reports · 2021Article
- Lysine-Specific Histone Demethylase 1A Regulates Macrophage Polarization and Checkpoint Molecules in the Tumor Microenvironment of Triple-Negative Breast Cancer.Frontiers in immunology · 2019Article
- Hoodwinking the Big-Eater to Prosper: The Salmonella-Macrophage Paradigm.Journal of innate immunity · 2019Review
- The Role of Phospholipase C Signaling in Macrophage-Mediated Inflammatory Response.Journal of immunology research · 2018Review
- Thymulin, free or bound to PBCA nanoparticles, protects mice against chronic septic inflammation.PloS one · 2018Article
- Protein kinase C theta is required for efficient induction of IL-10-secreting T cells.PloS one · 2017Article
- The role of IL-10 in Mycobacterium avium subsp. paratuberculosis infection.Cell communication and signaling : CCS · 2016Review
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe serine/threonine protein kinase C (PKC) theta has been firmly implicated in T cell-mediated immunity. Because its role in macrophages has remained undefined, we employed PKCtheta-deficient (PKCtheta (-/-)) mice in order to investigate if PKCtheta plays a role in macrophage-mediated immune responses during bacterial infections.
resultsOur results demonstrate that PKCtheta plays an important role in host defense against the Gram-negative, intracellular bacterium Salmonella typhimurium, as reflected both by markedly decreased survival and a significantly enhanced number of bacteria in spleen and liver of PKCtheta (-/-) mice, when compared to wild-type mice. Of note, albeit macrophages do not express detectable PKCtheta, PKCtheta mRNA expression was found to be profoundly upregulated during the first hours of lipopolysaccharide (LPS)/interferon-gamma (IFNgamma)-, but not IL-4-mediated cell polarization conditions in vitro. Mechanistically, despite expressing normal levels of classically activated macrophage (CAM) markers, PKCtheta-deficient CAMs expressed significantly higher levels of the anti-inflammatory cytokine IL-10 in vivo and in vitro when challenged with S. typhimurium or LPS/IFNgamma. Neutralization of IL-10 recovered immune control to S. typhimurium infection in PKCtheta-deficient macrophages.
conclusionsTaken together, our data provide genetic evidence that PKCtheta promotes a potent pro-inflammatory CAM phenotype that is instrumental to mounting protective anti-bacterial immunity. Mechanistically, PKCtheta exerts a host-protective role against S. typhimurium infection, and acts as an essential link between TLR4/IFNgammaR signaling and selective suppression of the anti-inflammatory cytokine IL-10 at the onset of CAM differentiation in the course of a bacterial infection.
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