Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells

Akinobu Takaki, M. Tatsukawa, Yoshiaki Iwasaki, K. Koike, Y. Noguchi, Hidenori Shiraha, K. Sakaguchi, E. Nakayama, K. Yamamoto

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Dendritic cells (DCs) in chronic hepatitis C patients display impaired function, although the details remain unclear. To investigate the hepatitis C virus (HCV) protein that has the most impact on DC function, we compared five recombinant proteins and seven HCV protein genes in modulating DC phenotype and function. Immature DCs (iDCs) were established from healthy donor peripheral blood monocytes with granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-4. Lipopolysaccharide was used to establish mature DCs (mDCs). Cells were then pulsed with HCV recombinant proteins or transfected with HCV plasmids and subsequently assayed for cell surface marker expression by flow cytometry. For cytokine and proliferative T-cell response analysis, DCs were cultured with autologous CD4 T cells and tuberculin purified protein derivative (PPD). Mean fluorescent intensity of CD86 was reduced in HCV protein-pulsed iDCs. Proliferative T-cell responses and Th1 cytokine concentrations were reduced with HCV nonstructural proteins (NS), particularly with HCV NS4. HCV nonstructural proteins, particularly NS4, change the iDC phenotype and reduce antigen-specific T-cell stimulatory function with Th1 cytokine reductions.

Original languageEnglish
Pages (from-to)555-562
Number of pages8
JournalJournal of Viral Hepatitis
Volume17
Issue number8
DOIs
Publication statusPublished - 2010

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Hepacivirus
Dendritic Cells
T-Lymphocytes
Cytokines
Proteins
Recombinant Proteins
Phenotype
hepatitis C virus NS4 protein
Tuberculin
Chronic Hepatitis C
Granulocyte-Macrophage Colony-Stimulating Factor
Blood Donors
Interleukin-4
Lipopolysaccharides
Monocytes
Flow Cytometry
Plasmids
Antigens

Keywords

  • dendritic cell
  • hepatitis C virus
  • T cell

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases
  • Virology
  • Medicine(all)

Cite this

Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells. / Takaki, Akinobu; Tatsukawa, M.; Iwasaki, Yoshiaki; Koike, K.; Noguchi, Y.; Shiraha, Hidenori; Sakaguchi, K.; Nakayama, E.; Yamamoto, K.

In: Journal of Viral Hepatitis, Vol. 17, No. 8, 2010, p. 555-562.

Research output: Contribution to journalArticle

Takaki, Akinobu ; Tatsukawa, M. ; Iwasaki, Yoshiaki ; Koike, K. ; Noguchi, Y. ; Shiraha, Hidenori ; Sakaguchi, K. ; Nakayama, E. ; Yamamoto, K. / Hepatitis C virus NS4 protein impairs the Th1 polarization of immature dendritic cells. In: Journal of Viral Hepatitis. 2010 ; Vol. 17, No. 8. pp. 555-562.
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