title: The response to TLR ligation of human CD16⁺CD14⁻ monocytes is weakly modulated as a consequence of persistent infection with the hepatitis C virus.
abstract: Little is known about the frequency and function of CD16(+)CD14(-) monocytes from chronic HCV patients. We observed that the absolute numbers and ratio of CD16(+)CD14(-) to CD14(+)CD16(-) monocytes were similar between chronic HCV patients and healthy individuals. Functionally, we found that CD16(+)CD14(-) monocytes are more responsive to TLR8-ligation and only weakly responsive to LPS stimulation in producing TNF as compared to CD14(+)CD16(-) monocytes. We found no overt impairment of the function of CD16(+)CD14(-) monocytes from patients, except for an augmented induction of MIP-1β-producing CD16(+)CD14(-) monocytes upon TLR4-ligation. However, the increased frequency of MIP-1β-producing CD16(+)CD14(-) monocytes was not associated with viral load, ALT or fibrosis level. Our findings indicate that, different from other infectious diseases, the frequency and function of CD16(+)CD14(-) monocytes are only minimally altered as a consequence of the persistent state of HCV infections, and our findings therefore do not suggest a role for CD16(+)CD14(-) monocytes in HCV pathogenesis.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.forename: Bi-Sheng
authors.initials: BS
authors.lastname: Liu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: de Knegt
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: André
authors.initials: A
authors.lastname: Boonstra
mesh_terms: D000328:Adult; D002452:Cell Count; D054407:Chemokine CCL4 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051200:Toll-Like Receptor 8 / Q000819:agonists / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D054407:Chemokine CCL4; D016207:Cytokines; D007093:Imidazoles; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D017452:Receptors, IgG; D051197:Toll-Like Receptor 4; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha; C402365:resiquimod