Monocytes Affect Natural Killer cell Antiviral IFN-γ Production in HCV Infection via Inflammasome-mediated IL-18 Secretion

IFN-γ production by Natural killer (NK) cells is attenuated in patients with chronic hepatitis C virus (HCV) infection. Here, we asked whether this impairment is NK cell-intrinsic or extrinsic. Hepatoma cells expressing luciferase-tagged subgenomic HCV replicons (Huh7/HCV-replicons) or their HCV-negative counterparts (Huh7) were co-cultured with NK cells in the presence or absence of other PBMC subsets. Antiviral activity, cytotoxicity, and cytokine production were assessed. NK cells exerted greater IFN-γ production (22% vs. 8% IFN-γ+ NK cells, p = 0.004; MFI 318 vs. 114, p < 0.05) when PBMC were co-cultured wit…