title: Differential expression of Toll-like receptors 7 & 8 mRNA in monocytes of patients with chronic hepatitis C infection: correlation with interferon and ribavirin treatment.
abstract: Toll-like receptors (TLRs) have been identified as key regulators of innate and adaptive immune responses in viral infection. The contribution of the host immune response to sustained virologic response is not clear in patients with chronic hepatitis C virus (HCV) infection. This study aimed to investigate the expression of TLRs 7 & 8 mRNA in monocytes of patients with chronic (HCV) infection showing different responses to interferon and ribavirin treatment. The study group was comprised of 21 chronic HCV infected patients. mRNA levels of TLRs 7 & 8 in monocytes were evaluated using real-time PCR before a 48-week treatment with pegylated interferon (PEG-IFN) alpha-2b and ribavirin. In addition, we studied TNF production in monocytes using three-color immunofluorescence and flow cytometry after TLRs 7 & 8 ligand (R848) stimulation. According to the virological outcome of the treatment, the infected patients were classified into nonresponders (NR) and sustained virological responders (SVR). The study determined that mRNA levels of TLRs 7 & 8 were significantly high in SVR compared to NR. Furthermore, after stimulation with R848 the median fluorescence intensity for TNF protein was significantly high in SVR compared to NR. Our data show that a differential mRNA expression of TLRs 7 & 8 is associated with different responses to IFN-based antiviral therapy in patients with chronic HCV. These findings suggest that the TLRs-expression profiles of monocytes from patients with chronic HCV may be useful biomarkers for IFN therapy.
authors.forename: Ghada
authors.initials: G
authors.lastname: Boghdadi
authors.forename: Waseem Mohamed
authors.initials: WM
authors.lastname: Seleem
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique / Q000379:methods; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000187:drug effects / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism* / Q000821:virology; D011092:Polyethylene Glycols / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000627:therapeutic use; D051199:Toll-Like Receptor 7 / Q000235:genetics*; D051200:Toll-Like Receptor 8 / Q000235:genetics*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D007093:Imidazoles; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; C495348:TLR7 protein, human; C495349:TLR8 protein, human; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C402365:resiquimod