Dendritic cells in the pathogenesis of viral hepatitis C

Abstract

Infection with hepatitis C virus (HCV) is a public health problem; it establishes a chronic course in most (up to 85%) infected patients and increases the risk for developing liver cirrhosis, hepatocellular carcinoma, and severe extrahepatic manifestations. The mechanisms of HCV persistence are largely related to the inefficient antiviral response of the host immune system. The effective clearance of the virus requires early activation of innate immune system together with the induction of a strong multiepitopic adoptive T cell response and long-term antiviral memory. Dendritic cells (DCs), which represent a heterogeneous population of antigen-presenting cells, contribute to the production of type I interferon, activate natural killer cells and induce adoptive immune response thus playing a major role in antiviral defense. In this case, DCs dysfunction in HCV-infection is considered to be the one of the mechanism that allows the virus to escape from the immune surveillance. The present review includes current data focusing on the role of DCs in the anti-HCV immune response and highlights a number of key issues related to the phenotypic and functional changes of various DC subpopulations in HCV-infection, the mechanisms of DC impairments and the prospects for treatment of chronic hepatitis C based on the use of ex vivo generated DCs.