Hepatitis C virus E2 and CD81 interaction may be associated with altered trafficking of dendritic cells in chronic hepatitis C.
Dendritic cells (DC) are crucially involved in the induction of immune responses; however, reports on DC functions in chronic hepatitis C are controversial. Function of DC includes proper cell trafficking between sites of infection and lympho-cellular compartments. Thus, we analyzed DC compartmentalization and changes in DC migration in hepatitis C virus (HCV)-infected patients. We found significantly lower numbers of circulating BDCA1+ and BDCA2+ DC in HCV(+) patients (n = 20) than in healthy controls (n = 12) (P < .05). Analyzing liver samples from HCV(+) patients (n = 15), HCV(-) controls (n = 15), and disease controls (n = 10), we demonstrated chronic hepatitis C to be associated with intrahepatic DC enrichment (P < .05). In vitro studies indicated that HCV E2-induced secretion of RANTES efficiently attracts CCR5(+) immature DC. Incubation of DC with sera derived from HCV(+) patients made DC unresponsive to CCL21, the chemokine recruiting DC to lymphoid tissues for T cell priming. Unlike attraction of CCR5+ DCs via RANTES, direct inhibition of DC migration in response to CCL21 was specific for patients with chronic hepatitis C and could be attributed to interaction of HCV E2 with CD81 on DC. In conclusion, migration of DC is markedly affected by interaction of HCV E2 with CD81. Failure of DC to recirculate to lymphoid tissue may be critically involved in impaired T cell priming during HCV infection.
Nattermann
Jacob
J
Department of Internal Medicine I, Rheinische Friedrich Wilhelms Universität Bonn, Germany. Jacob.Nattermann@ukb.uni-bonn.de
Zimmermann
Henning
H
Iwan
Agathe
A
von Lilienfeld-Toal
Marie
M
Leifeld
Ludger
L
Nischalke
Hans Dieter
HD
Langhans
Bettina
B
Sauerbruch
Tilman
T
Spengler
Ulrich
U
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism; D002465:Cell Movement; D054421:Chemokine CCL21; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D016174:Hepacivirus / Q000378:metabolism*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D008099:Liver / Q000166:cytology; D008297:Male; D008875:Middle Aged; D011991:Receptors, Virus / Q000378:metabolism*; D013601:T-Lymphocytes; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins / Q000378:metabolism* / Q000494:pharmacology
D015703:Antigens, CD; D000954:Antigens, Surface; C515478:CCL21 protein, human; C554798:CD81 protein, human; D054421:Chemokine CCL21; D018946:Chemokine CCL5; D019742:Chemokines, CC; D011991:Receptors, Virus; D060225:Tetraspanin 28; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus