Hepatic stellate cells, liver innate immunity, and hepatitis C virus

Chronic hepatitis C virus (HCV) infection can cause liver damage, ranging from mild to more severe conditions, such as fibrosis and cirrhosis. Hepatic stellate cell (HSC) activation is a key event in HCV-induced liver fibrosis. HSCs express several HCV coreceptors that interact with HCV proteins, promoting liver fibrogenesis. In addition, HSCs have the ability to engulf apoptotic bodies of hepatocytes induced by HCV and trigger a profibrogenic response. Recent studies have suggested that HSCs may play a novel role in the liver innate immunity. HSCs enhanced differentiation and accumulation of regulatory T cells. HSCs-activated natural killer cells could produce gamma-interferon that inhibits HCV replication. Importantly, HSCs possess functional Toll-like receptor-3 and retinoic acid-inducible gene I that can be activated by their ligands (poly I : C, 5'ppp-dsRNA), leading to the induction of interferon and inhibition of HCV replication in hepatocytes. These new observations highlight the importance of HSCs in liver immunity against HCV, which is the focus of this review paper.