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Cell Commun Signal. 2016 Jul 28;14(1):14. doi: 10.1186/s12964-016-0137-y.

Role of PKCtheta in macrophage-mediated immune response to Salmonella typhimurium infection in mice.

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Department for Pharmacology and Genetics, Division of Translational Cell Genetics, Peter Mayr Straße 1a, 6020, Innsbruck, Austria.
Department of Internal Medicine VI/Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University Innsbruck, Anichstraße 35, 6020, Innsbruck, Austria.
Department for Pharmacology and Genetics, Division of Translational Cell Genetics, Peter Mayr Straße 1a, 6020, Innsbruck, Austria.



The 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.


Our 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.


Taken 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.


IL-10; Innate immunity; Macrophage polarization; Protein kinase C theta; Salmonella typhimurium

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