Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide

Madera, Sharline; Rapp, Moritz; Firth, Matthew A.; Beilke, Joshua N.; Lanier, Lewis L.; Sun, Joseph C.

Type I IFN has long been observed to promote NK cell-mediated cytotoxicity (Biron et al., 1999) . In line with previous studies (Nguyen et al., 2002; Baranek et al., 2012) , we were able to detect a defect in granzyme B up-regulation by Ifnar −/− NK cells after MCMV infection (Fig. 3 B) . This diminished cytotoxicity of Ifnar −/− NK cells likely explains the reduced protection during lethal MCMV infection (Fig. 1 D) . In accordance with previous findings showing that type I IFN inhibits IFN-γ production by NK cells in a STAT1-dependent manner (Nguyen et al., 2000) , we observed a greater production of IFN-γ by Ifnar −/− NK cells when compared with WT NK cells after MCMV infection (Fig. 3 B) . Thus, the protection mediated by Ifnar −/− NK cells over the control group is likely a consequence of heightened IFN-γ production during viral challenge.