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.

With the hypothesis that type 1 IFN induction of NK cell IFN-␥ is in place to access low, regional levels of the cytokine as infections are initiated, studies were undertaken to examine responses at the earliest times of viral infection under immunocompetent conditions. The system used for study was intraperitoneal (i.p.) infection of C57BL/6 (B6) mice with lymphocytic choriomeningitis virus (LCMV) (7, 9, 16, 17) . This infection has been well characterized and is of relevance to the human condition because LCMV can cause significant morbidity and mortality, particularly in immunodeficient individuals (18) (19) (20) . The virus is a potent inducer of type 1 IFN, with systemic levels produced in serum and spleen for several days after i.p. infection (7, 9, 17) . In contrast, LCMV is a poor inducer of IL-12, with low to undetectable levels of the cytokine produced (8, 16) , and NK cell IFN-␥ expression is also low to undetectable in the serum and spleens of LCMV-infected mice (8, 9) . Because the initial site of virus entry is the peritoneal cavity, the studies focused on previously uncharacterized events at this location.