Decreased interferon-α production and impaired regulatory function of plasmacytoid dendritic cells induced by the hepatitis C virus NS 5 protein

Muhammad Amjad, Nahed Abdel-Haq, Muhammad Faisal, Mustafa Kamal, Varsha Moudgal

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

pDC are known to produce large amount of IFN-α/β in response to viruses, and act as a major link between the innate and adaptive immune response. This study concentrated on the interaction of human peripheral blood derived pDC with HCV NS3, NS4, and NS5 proteins, and their maturation, cytokine secretion and functional properties. It was shown that HCV NS5 interferes with CD40L induced maturation of pDC as indicated by decreased expression of CD83 and CD86 markers. CpG ODN stimulated HCV NS3 and NS5 treated pDC showed decreased production of IFN-α. In the case of NS3, IFN-α production was reduced to 126 pg/ml as compared to 245 pg/ml in controls (P < 0.01), and with NS5, IFN-α production was reduced to 92 pg/ml as compared to 238 pg/ml in controls (P < 0.05). In the presence of HCV NS5, the T cell stimulatory capacity of pDC was impaired, as indicated by decreased proliferation of T cells, and decreased production by the T cells of IFN-γ, which were down to 86 pg/ml as compared to 260 pg/ml in controls (P < 0.05). These results suggest that HCV NS5 impairs pDC function and is in agreement with several other in vivo studies indicating decreased numbers of, and dysfunctional pDC, in chronic HCV infected patients.

Original languageEnglish
Pages (from-to)499-507
Number of pages9
JournalMicrobiology and Immunology
Volume52
Issue number10
DOIs
StatePublished - Oct 2008

Keywords

  • Dendritic cells
  • Hepatitis C virus
  • Interferon-α
  • Nonstructural proteins

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