Type 1 Interferon Induction of Natural Killer Cell Gamma Interferon Production for Defense during Lymphocytic Choriomeningitis Virus Infection

Mack, Ethan A.; Kallal, Lara E.; Demers, Delia A.; Biron, Christine A.

The peritoneal responses reported here demonstrate that by being receptive to early type 1 IFN signaling with IFN-␥ production, NK cells can serve as sensors for and responders to the presence of viral pathogens. The studies surprisingly reveal a previously elusive role for NK cells in early defense against LCMV. In comparison to other viral infections in compartments outside the peritoneal cavity, LCMV has been shown to be relatively insensitive to the direct antiviral effects of NK cells (40) (41) (42) or IFN-␥ (43) . Our previous attempts to access NK cell IFN-␥ in defense against LCMV have shown that administration of IL-12 prior to infection can induce the response to result in under a 1-log decrease in splenic viral titers (44) . In this report, infection-induced IFN-␥, dependent on NK cells, was shown to proportionally limit viral burden at this first site of infection. Thus, though modest, there is a documented effect of the NK cells and IFN-␥ during LCMV infection. The mechanism for the antiviral effect mediated by IFN-␥ is not known. Given the rapid kinetics, it is likely to be a result of the activation of direct antiviral effects in infected cells or macrophages rather than enhancement of adaptive immune functions resulting from promoting major histocompatibility complex (MHC) class 1 expression or CD8 T cell effector functions (45) . It remains to be determined whether or not the NK cell IFN-␥ elicited by type 1 IFNs will be a more important first response in defense against other more sensitive viral infections and/or for promoting immunoregulatory functions.