Key Message
During viral infections anti-viral interferon (IFN) responses are induced. While type I IFNs rapidly enhance the expression of more than 250 genes, type II IFN (IFN-γ) balances the resulting immune response. IFN-γ is produced by innate immune cells such as NK cells and adaptive immune cells such as T cells. However, so far it was unclear which functions the innate and the adaptive IFN-γ have. To address the function of IFN-γ from different cellular origins we generated IFN-γOFF mice, in which the endogenous IFN-γ gene function can be reconstituted in a Cre-dependent manner. By intercrossing IFN-γOFF mice with Ncr1-Cre mice that express Cre selectively in Ncr1+ innate cell subsets such as NK cells, IFN-γNcr1-ON mice were obtained. Such mice survived infection with vaccinia virus. Thus, the innate IFN-γ was sufficient to restore cytokine responses that supported normal myeloid cell distribution and survival.
Translational perspective
This newly generated mouse model allows the analysis of innate versus adaptive IFN-γ responses in vivo. This model will be highly relevant to better understand many other infections, as well as models of autoimmunity and cancer.