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

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


Background: 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.

Results: 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.

Conclusions: 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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • Macrophage Activation
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Kinase C-theta
  • Salmonella Infections / immunology*
  • Salmonella typhimurium / immunology


  • Isoenzymes
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma
  • Prkcq protein, mouse
  • Protein Kinase C
  • Protein Kinase C-theta