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J Gen Virol 89 (2008), 1243-1253; DOI 10.1099/vir.0.83517-0

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Altered chemotactic response of myeloid and plasmacytoid dendritic cells from patients with chronic hepatitis C: role of alpha interferon

Vito R. Cicinnati1,2, Jinyu Kang1, Georgios C. Sotiropoulos2, Philip Hilgard1, Andrea Frilling2, Christoph E. Broelsch2, Guido Gerken1 and Susanne Beckebaum1,2

1 Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Germany
2 Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg-Essen, Germany

Correspondence
Susanne Beckebaum
susanne.beckebaum{at}uni-due.de

Dendritic cell (DC) frequencies in the blood of patients with chronic hepatitis C virus (HCV) infection have been shown to be reduced significantly compared with those in healthy individuals. There is a further reduction of circulating myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) in HCV patients receiving alpha interferon (IFN-{alpha})-based antiviral therapy. Altered homing behaviour of DCs may be a possible mechanism for their ‘loss’ in peripheral blood in these clinical conditions. Systemic chemokine levels were measured by ELISA. Phenotypes and migratory properties of MDCs and PDCs from HCV patients were analysed by flow cytometry and chemotaxis assay. Compared with healthy controls, HCV patients had increased serum levels of inflammatory and constitutively expressed chemokines. Spontaneously generated MDCs from HCV patients were less mature, and both MDCs and PDCs showed intrinsic activation of receptors for inflammatory chemokines, thus suggesting an increased propensity to migrate towards inflammatory sites. IFN-{alpha} treatment in vitro induced MDC maturation and skewed the migratory response of both MDCs and PDCs towards chemokines expressed constitutively in secondary lymphoid organs. In conclusion, our results hint at altered homing behaviour of DCs during chronic HCV infection. IFN-{alpha} therapy may redirect DC migration from inflamed hepatic portal areas towards secondary lymphoid tissue.







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