Quantification and functional analysis of plasmacytoid dendritic cells in patients with chronic hepatitis C virus infection.

Plasmacytoid dendritic cells (PDCs) are the major producers of interferon (IFN)- alpha within peripheral blood mononuclear cells (PBMCs). We analyzed whether chronic hepatitis C virus (HCV) infection could be linked to a defective function or number of PDCs. We evaluated the capacity of PBMCs from 5 cohorts of subjects to produce IFN- alpha after viral stimulation. We concomitantly analyzed the frequency of PDCs and the levels of IFN- alpha transcripts within the PBMCs from the same cohorts. PBMCs from patients with chronic HCV infection receiving antiviral therapy displayed a reduced capacity to release IFN- alpha, compared with those from healthy individuals, those from long-term responders to therapy, and those from nontreated patients. This defect was significantly correlated with the percentage of PDCs. In addition, PDCs from patients with chronic HCV infection receiving therapy displayed a reduced intrinsic capacity to produce IFN- alpha, which could be linked to the level of IFN- alpha transcripts. Our observations point to an effect of the therapy on either the survival or the localization of PDCs, rather than a direct detrimental effect due to the viral infection during chronic HCV infection.