ID: 249: Hepatic macrophage regulation of Hepatitis C virus infection

Abstract

Currently, over 200 million people are chronically infected with Hepatitis C virus (HCV), which is the leading cause of end stage liver diseases. In order to mitigate the HCV pandemic, better understanding of the immune response is critical as it determines the clinical outcome, whether the host spontaneously clears the pathogen or transitions to chronic infection. The innate immunity during acute infection is the frontline defense, which is initiated by the interaction between viral product and host Pattern Recognition Receptors (PRRs). The PRR recognition of infection occurs in both infected hepatocytes as well as surrounding professional innate immune cells. Hepatic macrophages reside adjacent to hepatocytes and are expected to be exposed to HCV particles as well as infected cells. To date, the role of macrophage in acute HCV infection has been poorly understood. Here, we investigated the macrophage response to acute exposure to HCV. Our results indicated that phagocytosis by macrophages plays a significant role in the clearance of HCV. In addition, we found that the phagocytosis of HCV triggers robust antiviral innate immune responses, which potently restrict the viral replication in hepatocytes. However, we also found that the macrophage provokes inflammatory responses when in contact with the infected cells. Collectively, these results suggest that the hepatic macrophage is a critical modulator of diseases presentation in both suppression of HCV infection of hepatocytes at the initial encounter and governing of hepatic inflammation thereafter. In conclusion, our results provide novel insights on the critical interplay between the hepatic macrophage and HCV.