Differential dysfunction in dendritic cell subsets during chronic HCV infection

Lynn Averill, William M. Lee, Nitin J. Karandikar

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Hepatitis C virus (HCV) infection is a leading cause of chronic liver disease with over 200 million individuals infected worldwide. The vast majority of acutely infected humans develop chronic infection, which is characterized by attenuated antiviral T-cell responses. The mechanisms leading to such attenuation/suppression are poorly understood. It has been proposed that dysfunction of antigen-presenting cells (APC) may underlie the downregulation of antiviral immune responses. However, studies using bulk or in vitro-derived APC populations have resulted in conflicting reports. In this study, we evaluated the functional and immunophenotypic features of ex vivo-purified dendritic cell (DC) subsets during chronic HCV infection. We found that plasmacytoid DC (PDC) from HCV-infected patients (HCV-PDC) showed a striking deficit in IFN-α production in response to CpG stimulation. In addition, we found that myeloid DC (MDC) from these patients showed a diminished capacity to induce a mixed lymphocyte response (MLR), correlating with lower levels of HLA-DR and CD86 expression and higher IL-10 production in response to poly-IC stimulation. In contrast, HCV-PDC showed increased ability to stimulate an MLR. Of note, within the HCV-PDC preparation, we noted a distinctly expanded DC subset that expressed some markers of MDC, but showed significantly lower HLA-DR and CD86 expression, suggesting an expansion of DC at an immature/intermediate stage of differentiation. Our studies demonstrate distinct and contrasting dysfunctional features in DC subsets and underscore the importance of evaluating APC subpopulations separately.

Original languageEnglish (US)
Pages (from-to)40-49
Number of pages10
JournalClinical Immunology
Volume123
Issue number1
DOIs
StatePublished - Apr 2007

Keywords

  • Dendritic cell
  • Hepatitis C
  • IFN-alpha
  • MDC
  • PDC

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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