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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.

The induction of a strong multi-epitope T-cell response against hepatitis C virus (HCV) plays an important role in eliminating the virus, whereas adoptive response deficiency contributes to chronic and rapid progression of HCV-infection. Since dendritic cells (DCs) are capable of priming naive T lymphocytes and induce an effective immune response, the use of DC-based vaccines to enhance the HCV-specific T cell response is considered as a new approach to treatment of chronic hepatitis C (CHC). The ability of DCs generated from monocytes in the presence of interferon-α and loaded with recombinant HCV proteins Core (1–120) and NS3 (1192–1457) to induce an antigen-specific cellular response in healthy donors and patients with CHC was investigated. The immune response was assessed by proliferative activity and Th1 (IFNγ)/Th2 (IL-4, IL-6) production in mononuclear cells (MNC) cultures, and activation of cytotoxic T-lymphocytes in the degranulation test. We demonstrated that the primary antigen-specific response in MNC cultures of seronegative donors was detected better by stimulation of DCs, loaded with both antigens (DCCore /NS3) than when loaded with a single protein. DCCore/NS3 induced the proliferative response and degranulation of CD8+ T cells in MNC cultures of all tested donors, and in 50% (5/10) cases — IFNγ production. Similarly to donor DCs, DCCore/NS3 of patients with CHC induced a proliferative response in most cases (86%) and IFNγ production in 57% cases. At the same time, the activation of cytotoxic T cells in patients was less frequent (patients vs donors 57 and 100%, respectively), which could be partly due to increased spontaneous degranulation of CD8+ T cells in some patients. The obtained data testify the possibility of using vaccines based on interferon-α-induced DCs for the prevention and treatment of chronic HCV infection.