Monocyte-derived dendritic cells from chronic HCV patients are not infected but show an immature phenotype and aberrant cytokine profile

Liver Int. 2007 Sep;27(7):944-53. doi: 10.1111/j.1478-3231.2007.01507.x.

Abstract

Background: Chronic hepatitis C virus (HCV) infection is characterized by an insufficient immune response, possibly owing to impaired function of antigen-presenting cells such as myeloid dendritic cells (DCs). Therapeutic vaccination with in vitro generated DCs may enhance the immune response. Subsets of DCs can originate from monocytes, but the presence of HCV in monocytes that develop into DCs in vitro may impair DC function. Therefore, we studied the presence of HCV RNA in monocytes and monocyte-derived DCs from chronic HCV patients.

Methods: Monocytes were cultured with granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) for 6 days, and then with GM-CSF, IL-4, tumour necrosis factor-alpha (TNF-alpha), prostaglandin E2, IL-1beta and IL-6 for 2 days to generate mature DCs. HCV RNA was assessed by polymerase chain reaction. Surface molecules were assessed by flow cytometry. Cytokine production was assessed by cytokine bead array.

Results: HCV RNA was present in monocytes in 11 of 13 patients, but undetectable in mature DCs in 13 of 13 patients. The morphology of patient DCs was comparable with DCs from healthy controls, but the percentage of cells expressing surface molecules CD83 (P=0.001), CD86 (P=0.023) and human leucocyte antigen-DR (P=0.028) was lower in HCV patients. Compared with control DCs, patient DCs produced enhanced levels of IL-10 (P=0.0079) and IL-8 (P=0.0079), and lower levels of TNF-alpha (P=0.032), IL-6 (P=NS) and IL-1beta (P=0.0079). Patient and control DCs did not produce IL-12.

Conclusions: Monocyte-derived DCs from chronic HCV patients are not infected but show an immature phenotype and aberrant cytokine profile.

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • B7-2 Antigen / metabolism
  • Case-Control Studies
  • Cells, Cultured
  • Cytokines / metabolism*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / virology*
  • Female
  • HLA-DR Antigens / metabolism
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / metabolism*
  • Humans
  • Immunity, Cellular
  • Immunity, Innate
  • Immunoglobulins / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Lymphocytes / virology
  • Male
  • Membrane Glycoproteins / metabolism
  • Middle Aged
  • Monocytes / immunology
  • Monocytes / metabolism
  • Monocytes / virology*
  • Phenotype
  • RNA, Viral / blood*
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, CD
  • B7-2 Antigen
  • CD83 antigen
  • CD86 protein, human
  • Cytokines
  • HLA-DR Antigens
  • IL10 protein, human
  • IL6 protein, human
  • Immunoglobulins
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Membrane Glycoproteins
  • RNA, Viral
  • Tumor Necrosis Factor-alpha
  • Interleukin-10