Functional changes, increased apoptosis, and diminished nuclear factor-kappaB activity of myeloid dendritic cells during chronic hepatitis C infection.
Approximately 70% of patients infected with hepatitis C virus (HCV) develop chronic infections, which have been reported to be caused by impaired specific T-cell responses. Myeloid dendritic cells (mDCs) are important antigen-presenting cells that regulate T-cell responses, however their role during chronic hepatitis C (CHC) is not fully understood. In this study, we found that the ability of mDCs to stimulate T-cell responses was impaired in CHC patients. Furthermore, mDCs from CHC patients underwent apoptosis at a higher rate than mDCs from healthy donors. Nuclear factor-kappaB activity, which is critical for mDC function and apoptosis prevention, was diminished in mDCs from CHC patients. In conclusion, mDCs from CHC patients demonstrated functional changes with increased apoptosis, and diminished nuclear factor-kappaB activity. These changes may contribute to the impaired specific T-cell responses in CHC patients.
Zhao
Li
L
Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada. lzl@ualberta.ca
Shields
Justin
J
Tyrrell
D Lorne
DL
D017209:Apoptosis; D051940:B7-2 Antigen / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D022423:Myeloid Cells / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism
D051940:B7-2 Antigen; D006684:HLA-DR Antigens; D020672:I-kappa B Proteins; D016328:NF-kappa B