Natural Killer (NK) cells serve as an important source of proinflammatory cytokines early during infection. Hypothesizing that Yersinia enterocolitica might interact with and inactivate NK cells, we examined NK cell-Y. enterocolitica interactions in vitro and in vivo. Y. enterocolitica adheres to NK cells in an Invasin dependent manner and inhibits NK cell cytotoxicity and IFN-γ production induced by IL-12+IL-18 or IL-12 alone. YopP, an acetyltransferase known to inhibit MAPK and NFκB signaling, suppresses IL-12 and IL-12+IL-18 mediated IFN-γ production in NK cells by inhibiting phosphorylation of Tyk2 and STAT4 in addition to MAPK. YopP inhibits induction of all genes whose expression is induced by IL-12+IL-18 in NK cells. Y. enterocolitica-mediated adherence to and inactivation of NK cells also occurs after infection in vivo. Thus, we present the first report of a bacterial pathogen inactivating NK cells, and report interaction with Tyk2-STAT4 signaling as a novel function of YopP.
Keywords: Host pathogen interaction; Infection immunology; Susceptibility to infection.
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