title: Intact dendritic cell pathogen-recognition receptor functions associate with chronic hepatitis C treatment-induced viral clearance.
abstract: Although studies have addressed the exhaustion of the host's immune response to HCV and its role in treatment, there is little information about the possible contribution of innate immunity to treatment-induced clearance. We hypothesized that because intact myeloid dendritic cell (MDC) pathogen sensing functions are associated with improved HCV-specific CD8+ T cell functionality in some chronically infected patients, it might enhance HCV clearance rate under standard interferon therapy. To investigate this hypothesis, TLR-induced MDC activation and HCV-specific CD8+ T cell response quality were monitored longitudinally at the single-cell level using polychromatic flow cytometry in chronically infected patients undergoing interferon therapy. We correlated the immunological, biochemical and virological data with response to treatment. We demonstrate that the clinical efficacy of interferon-induced viral clearance is influenced by the extent to which HCV inhibits MDC functions before treatment, rather than solely on a breakdown of the extrinsic T cell immunosuppressive environment. Thus, viral inhibition of MDC functions before treatment emerges as a co-determining factor in the clinical efficacy of interferon therapy during chronic HCV infection.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montréal, Québec, Canada.
authors.forename: Ian Gaël
authors.initials: IG
authors.lastname: Rodrigue-Gervais
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montréal, Québec, Canada.
authors.forename: Hawley
authors.initials: H
authors.lastname: Rigsby
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montréal, Québec, Canada.
authors.forename: Loubna
authors.initials: L
authors.lastname: Jouan
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montréal, Québec, Canada; Département de Médecine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Willems
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montréal, Québec, Canada; Département de Médecine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lamarre
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D022423:Myeloid Cells / Q000276:immunology; D011092:Polyethylene Glycols / Q000627:therapeutic use; D051192:Receptors, Pattern Recognition / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use; D051193:Toll-Like Receptors / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D051192:Receptors, Pattern Recognition; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a