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 IFNs provide a potent line of antiviral defense through direct and indirect effects on cells of the immune system, leading to their activation and effector function (Biron, 2001; González-Navajas et al., 2012) and resulting in the attenuation of viral replication (Müller et al., 1994) . IFN-α and IFN-β are members of the type I IFN family. All members of the type I IFN family signal through a ubiquitously expressed heterodimeric receptor that is composed of the IFN-α receptor 1 (IFN AR1) and IFN AR2 chains. Type I IFNs act directly on NK cells to promote their activation, cell cycle entry, and cytotoxic function during viral infection (Biron et al., 1984; Orange and Biron, 1996; Biron, 2001; Nguyen et al., 2002; Martinez et al., 2008; Baranek et al., 2012; Fortin et al., 2013) . However, the experimental systems used in previous studies-direct infection of IFN receptor-deficient mice or WT mice with IFN neutralization-are complicated by potential differences in the degree of inflammation, effects on many cell types, and viral load. Thus, the direct influence of type I IFN on effector and long-lived antiviral NK cell responses, while eliminating pleotropic effects on other cells, has not been investigated previously.