title: HCV core and NS3 proteins manipulate human blood-derived dendritic cell development and promote Th 17 differentiation.
abstract: Hepatitis C virus (HCV) chronic infection is characterized by low-level or undetectable cellular immune response against HCV antigens. HCV proteins affect various intracellular events and modulate immune responses, although the mechanisms that mediate these effects are not fully understood. In this study, we examined the effect of HCV proteins on the differentiation of human peripheral blood monocytes to dendritic cells (DCs). The HCV core (HCVc) and non-structural 3 (NS3) proteins inhibited the expression of CD1a, CD1b and DC-SIGN during monocyte differentiation to DCs, while increasing some markers characteristic of macrophages (CD14 and HLA-DR) and also PD-L1 expression. Meanwhile, HCVc and NS3 could induce differentiating monocytes to secrete IL-10. However, anti-IL-10 mAb could not reverse HCVc and NS3 inhibition of monocyte differentiation into DCs. The HCVc and NS3 proteins increased IL-6 secretion both in immature and in fully differentiated DCs and also promoted CD4+ T-cell IL-17 production. Since T(h) 17 cells are active in many examples of immunopathology, these effects may contribute to HCV autoimmune responses in chronically infected patients.
authors.affiliation: Department of Surgery, Division of Solid Organ Transplantation and Hepatobiliary Surgery, University of Rochester Medical Center, Rochester, NY 14642, USA. zhengkun_tu@urmc.rochester.edu
authors.forename: Zhengkun
authors.initials: Z
authors.lastname: Tu
authors.forename: Heli K
authors.initials: HK
authors.lastname: Hamalainen-Laanaya
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nishitani
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kuroki
authors.forename: Ian Nicholas
authors.initials: IN
authors.lastname: Crispe
authors.forename: Mark S
authors.initials: MS
authors.lastname: Orloff
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology*; D018936:Hepatitis C Antigens / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D015703:Antigens, CD; D018936:Hepatitis C Antigens; D016753:Interleukin-10; D015850:Interleukin-6; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases