Is hepatitis C virus infection of dendritic cells a mechanism facilitating viral persistence?
More than 170 million people worldwide are chronically infected with hepatitis C virus (HCV), which is a major cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Impaired T-cell reactivity to HCV, a hallmark of inefficient adaptive immunity, is believed to be responsible for the high propensity of HCV to cause chronic infection. Dendritic cells are the most potent antigen-presenting cells and many viruses affect various dendritic cell functions. Data suggest that such changes induced by HCV may have an important role in viral persistence. HCV has been shown to bind to dendritic cells, although viral replication within these cells occurs at a very low level. Dendritic cells from people with chronic HCV infection are impaired in their capacity to stimulate T cells. This impairment may be a consequence of changes in the expression of major histocompatibility complex and costimulatory molecules on its surface, as well as in the production of cytokines such as interleukin 12. In addition, hepatic dendritic cells may be affected by the tolerogenic microenvironment of the liver, possibly generating dendritic cells that promote regulatory T cells, which suppress the cellular immune response mounted against HCV.
Pachiadakis
Ioannis
I
Institute of Hepatology, Department of Medicine, Windeyer Institute of Medical Sciences, University College London, London, UK.
Pollara
Gabriele
G
Chain
Benjamin M
BM
Naoumov
Nikolai V
NV
D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology / Q000821:virology; D016174:Hepacivirus / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology