Selective impairments in dendritic cell-associated function distinguish hepatitis C virus and HIV infection.
Impaired APC functions may play important roles in chronicity of hepatitis C virus (HCV) and HIV infections. To investigate the separate and combined effects of HCV and HIV infection on immature dendritic cells (DCs), we evaluated myeloid-derived DC (MDC) and plasmacytoid-derived DC (PDC) frequencies and functions, measured by Toll-like receptor ligand-induced IFN-alpha and IL-12, in healthy controls and subjects with chronic HCV, HIV, and HCV-HIV infection. To evaluate the relation between innate and adaptive immunity, we measured HCV-specific IFN-gamma-producing T cell frequency. MDC frequencies tended to be reduced in HIV infection (1.8-fold), while PDC frequencies were minimally reduced in HCV infection (1.4-fold). In contrast, a striking reduction in non-PDC-associated IFN-alpha production was observed in HIV-infected subjects (17-fold), while PDC-associated IFN-alpha production was markedly reduced in HCV-infected subjects (20-fold). Both non-PDC and PDC functions were impaired in HCV-HIV coinfection. MDC-associated IL-12 production was markedly reduced in both HCV and HIV-infected subjects (over 10-fold). Functional defects were attenuated with slowly progressive HIV infection. The proportion of subjects with HCV-specific T cell responses, and the number of Ags recognized were reduced in HCV-HIV subjects as compared with HCV singly infected subjects. A positive association was observed between MDC-associated IL-12 production and HCV-specific T cell frequency in HCV-infected subjects. These results indicate that immature DC function is dysregulated in HIV and HCV infections, but differentially, and that these defects are attenuated in slowly progressive HIV infection. These selectively different impairments may contribute to the reduced adaptive immune response to HCV in HCV-HIV coinfection.
Anthony
Donald D
DD
Department of Medicine, Veterans Administration Medical Center, Center for AIDS Research, and University Hospitals of Cleveland, Case Western Reserve University, Cleveland, OH 44106, USA. dda3@po.cewru.edu
Yonkers
Nicole L
NL
Post
Anthony B
AB
Asaad
Robert
R
Heinzel
Frederick P
FP
Lederman
Michael M
MM
Lehmann
Paul V
PV
Valdez
Hernan
H
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018899:CpG Islands / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology; D006526:Hepatitis C / Q000276:immunology* / Q000473:pathology; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D007970:Leukopenia / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011237:Predictive Value of Tests
C408982:CPG-oligonucleotide; D018984:Epitopes, T-Lymphocyte; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D018664:Interleukin-12; D011070:Poly I-C