Control of HCV Infection by Natural Killer Cells and Macrophages

Host defense against invading pathogens within the liver is dominated by innate immunity. Natural killer (NK) cells have been implicated at all stages of hepatitis C virus (HCV) infection, from providing innate protection to contributing to treatment-induced clearance. Decreased NK cell levels, altered NK cell subset distribution, activation marker expression, and functional polarization toward a cytolytic phenotype are hallmarks of chronic HCV infection. Interferon alpha (IFN-alpha) is a potent activator of NK cells; therefore, it is not surprising that NK cell activation has been identified as a key factor associated with sustained virological response (SVR) to IFN-alpha-based therapies. Understanding the role of NK cells, macrophages, and other innate immune cells post-SVR remains paramount for prevention of disease pathogenesis and progression. Novel strategies to treat liver disease may be aimed at targeting these cells.