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.

To further uncover the mechanism behind NK cellmediated fratricide, we investigated NKp46 and NK group 2 member D (NKG2D) triggering in NK cells as potential activating signals involved in the killing of Ifnar −/− NK cells during viral infection. Because NKp46 has been suggested to promote NK cell-mediated killing of CD8 + T cells unable to sense type I IFNs (Crouse et al., 2014) , we tested whether this receptor contributed to NK cell-mediated fratricide using Ncr1 gfp/gfp mice in which the Ncr1 gene, which encodes protein NKp46, is deleted. Equal numbers of WT and Ifnar −/− NK cells were cotransferred into WT and Ncr1 gfp/gfp hosts that were then infected with LCMV. Similar to WT hosts, Ncr1 gfp/gfp hosts exhibited a loss of NK cells unable to sense type I IFN during viral infection (Fig. 5 B) , indicating that NKp46 does not play a role in NK cell-mediated killing of Ifnar −/− NK cells.