Altered chemotactic response of myeloid and plasmacytoid dendritic cells from patients with chronic hepatitis C: role of alpha interferon.
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.
Cicinnati
Vito R
VR
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg-Essen, Germany.|Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Germany.
Kang
Jinyu
J
Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Germany.
Sotiropoulos
Georgios C
GC
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg-Essen, Germany.
Hilgard
Philip
P
Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Germany.
Frilling
Andrea
A
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg-Essen, Germany.
Broelsch
Christoph E
CE
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg-Essen, Germany.
Gerken
Guido
G
Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Germany.
Beckebaum
Susanne
S
Department of General, Visceral and Transplantation Surgery, University Hospital Essen, University of Duisburg-Essen, Germany.|Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Germany.
D000328:Adult; D000368:Aged; D054443:Cell Migration Assays; D002465:Cell Movement; D002633:Chemotaxis; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged
D016207:Cytokines; D016898:Interferon-alpha