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

Overview of attention for article published in Cell Communication and Signaling, July 2016
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Title
Role of PKCtheta in macrophage-mediated immune response to Salmonella typhimurium infection in mice
Published in
Cell Communication and Signaling, July 2016
DOI 10.1186/s12964-016-0137-y
Pubmed ID
Authors

Christa Pfeifhofer-Obermair, Karin Albrecht-Schgoer, Sebastian Peer, Manfred Nairz, Kerstin Siegmund, Victoria Klepsch, David Haschka, Nikolaus Thuille, Natascha Hermann-Kleiter, Thomas Gruber, Günter Weiss, Gottfried Baier

Abstract

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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 23%
Student > Bachelor 3 14%
Professor 1 5%
Other 1 5%
Student > Master 1 5%
Other 3 14%
Unknown 8 36%
Readers by discipline Count As %
Agricultural and Biological Sciences 3 14%
Medicine and Dentistry 3 14%
Immunology and Microbiology 3 14%
Biochemistry, Genetics and Molecular Biology 2 9%
Social Sciences 1 5%
Other 1 5%
Unknown 9 41%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 29 July 2016.
All research outputs
#20,336,685
of 22,881,964 outputs
Outputs from Cell Communication and Signaling
#923
of 997 outputs
Outputs of similar age
#320,219
of 365,664 outputs
Outputs of similar age from Cell Communication and Signaling
#5
of 7 outputs
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