Infection and dysfunction of circulating blood dendritic cells and their subsets in chronic hepatitis C virus infection

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Abstract
To understand interactions between dendritic cells (DCs) and viruses, in vitro-cultured monocyte-derived DCs are usually used for functional analyses. However, several recent studies indicate that circulating blood DCs are different from monocyte-derived DCs, both phenotypically and functionally. Indeed, circulating DCs act as functional antigen-presenting cells in vivo. This study was conducted to evaluate the function of circulating blood DCs in patients with chronic hepatitis C and to examine whether circulating DCs from these patients were infected by hepatitis C virus (HCV). The phenotypes and biological functions of circulating DCs from patients with chronic hepatitis C (n = 27), patients with non-HCV chronic liver disease (n = 7), and normal volunteers (n = 13) were analyzed. The presence of the HCV genome sequence in circulating blood DCs and in subsets of circulating DCs (myeloid DCs and plasmacytoid DCs) in patients with chronic hepatitis C was assessed. The stimulatory capacity of circulating DCs was significantly reduced in patients with chronic hepatitis C compared to patients with non-HCV chronic liver diseases and normal controls (P < 0.01). HCV RNA was identified in the overall population of circulating DCs, and in myeloid DCs and plasmacytoid DCs. Nucleotide sequences of the 5′ non-coding region of HCV RNA showed marked differences between paired samples of circulating DCs and sera from the same patients. Our results indicate the dysfunction and infection of circulatory blood DCs in chronic HCV infection. This may compromise the capacity of patients with hepatitis C to induce an effective antiviral immune response.

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