The role of PKCθ in Francisella tularensis infection in mice (164.4)

Abstract

Abstract Francisella tularensis is a facultative intracellular bacteria that causes tularemia in animals and humans. F. tularensis is highly virulent and can be lethal. T cells play a critical role in Francisella immunity. It has been shown that mice succumb to sublethal infections when all T cells are depleted; however individual subsets including CD4, CD8 and an unusual CD4-CD8-NK1.1- population can be protective. While T cells control infection by producing IFNγ and TNFα, other less well-characterized mechanisms also play a role. PKCθ is a protein kinase involved in T cell activation; PKCθ is important in IFNγ production and PKCθ-/- mice are protected against both TH1 and TH2 mediated diseases. To investigate the role of PKCθ in F. tularensis infection, we infected wild-type C57Bl/6 (WT) mice and B6.PKCθ-/- mice with a lethal dose of LVS (live vaccine strain) which is commonly used to study F. tularensis infection. While WT mice died within 2 weeks of infection, surprisingly, over 50% of the PKCθ-/- mice survived past 3 weeks. We found that infected PKCθ-/- mice had more CD4-CD8- T cells in liver and lung than WT mice. In contrast, PKCθ-/- mice had fewer CD4+ T cells in lymph nodes, spleen, liver, and lung. We found no difference in numbers of activated T cells in liver and lung of infected WT and PKCθ-/- mice. These results show that PKCθ may be important in the expansion of CD4+ and CD4-CD8- T cell subtypes and this shift in the absence of PKCθ may protect against LVS infection.