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

Abstract

Background: 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).

Methods: 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.

Results: 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.

Conclusions: 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.