Type I IFN activates NK cell IFN-γ production through the stimulation of IL-18 production in inflammatory monocytes during vaginal HSV-2 infection. Rapidly after HSV-2 infection, type I IFN is produced in the vaginal mucosa. Type I IFN induces CCL2 production from a cell type or types and recruits inflammatory monocytes to the site of infection. Type I IFN binds IFNAR on inflammatory monocytes and signals through IRF9 to induce their release of IL-18. IL-18 then ligates to IL-18R on NK cells to induce their production of IFN-γ.