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.

To characterize responses at the earliest times after infections, lavage fluids and cells were collected from peritoneal cavities of B6 mice that had been uninfected or infected i.p. with 5 ϫ 10 4 PFU LCMV at the indicated times prior to harvest. The fluids were tested to evaluate cytokines released at the site. The IFN-␥ levels were measured using a cytometric bead assay (CBA). Low but consistently detectable levels of IFN-␥ were found peaking at 30 h after LCMV infection (Fig. 1A) . Enzyme-linked immunosorbent assays (ELISAs) were used to measure IFN-␣ and IFN-␤. In contrast to the reported extended kinetics of systemic levels of these cytokines (7, 9, 17) as well as the type 1 IFNs detected through 48 h after infection in serum samples taken from mice used for these experiments (data not shown), concentrations of IFN-␣ and IFN-␤ in the peritoneum reached their peak values of 340 and 69 pg/ml, respec-tively, at 30 h after challenge and were sharply confined to the 6-h periods surrounding that point (Fig. 1A) . The levels of IL-12p70, a known inducer of IFN-␥, were acquired from the CBAs. All samples were below the limit of detection for the assay, with no detectable levels in a large majority of samples isolated after 20 to 48 h of infection (Fig. 1A) . Thus, the peritoneal cytokine responses to LCMV infection include early induction of IFN-␥, with kinetically overlapping IFN-␣ and IFN-␤ production, but undetectable IL-12.