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.

Type 1 IFN responsiveness is required for induction of NK cell IFN-␥ expression. Because induction of the biologically active IL-12p70 heterodimer can be accompanied by higher-level IL-12p40 subunit production (8), representative lavage samples from 0, 24, 30, 36, 40, and 48 h following LCMV infection were tested in an ELISA for the subunit. Consistent with our earlier studies (8) , all samples had IL-12p40 levels at or below the limit of detection for the assay (data not shown). To determine if biologically relevant IL-12 was induced below detection limits, uninfected and LCMV-infected mice were treated with control antibody or anti-IL-12p40 antibody neutralizing the function of biologically active IL-12p70 (8) . As a positive control for an IL-12induced IFN-␥ response (21, 22) , mice were given lipopolysaccharide (LPS) i.p. at 6 h prior to harvest. In comparison to LCMV infection, LPS treatment induced higher levels of IFN-␥ in lavage fluids ( Fig. 2A) and higher proportions of NK cells expressing IFN-␥ (Fig. 2B) . The enhanced response to LPS was blocked by the anti-IL-12 treatment. In contrast, the IFN-␥ response to LCMV infection was resistant to the anti-IL-12 treatment ( Fig. 2A and B) . Thus, IL-12 is not required for the NK cell IFN-␥ response elicited by the virus.