HCV core and NS3 proteins manipulate human blood-derived dendritic cell development and promote Th 17 differentiation

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...

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Bibliographic Details
Published in:International immunology 2012-02, Vol.24 (2), p.97-106
Main Authors: Tu, Zhengkun, Hamalainen-Laanaya, Heli K., Nishitani, Chiaki, Kuroki, Yoshio, Crispe, Ian Nicholas, Orloff, Mark S.
Format: Article
Language:English
Subjects:
Antigens, CD - immunology
Cell Differentiation - immunology
Cells, Cultured
Dendritic Cells - immunology
Gene Expression Regulation - immunology
Hepacivirus - immunology
Hepatitis C Antigens - immunology
Hepatitis C, Chronic - immunology
Humans
Immunomodulation
Interleukin-10 - immunology
Interleukin-10 - metabolism
Interleukin-6 - secretion
Th17 Cells - immunology
Viral Core Proteins - immunology
Viral Nonstructural Proteins - immunology
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Summary: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 Th 17 cells are active in many examples of immunopathology, these effects may contribute to HCV autoimmune responses in chronically infected patients.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/dxr104