Hepatitis C virus and ethanol alter antigen presentation in liver cells

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations

Abstract

Alcoholic patients have a high incidence of hepatitis C virus (HCV) II infection. Alcohol consumption enhances the severity of the HCV disease course and worsens the outcome of chronic hepatitis C. The accumulation of virally infected cells in the liver is related to the HCV-induced inability of the immune system to recognize infected cells and to develop the immune responses. This review covers the effects of HCV proteins and ethanol on major histocompatibility complex (MHC) class I - and class II -restricted antigen presentation. Here, we discuss the liver which functions as an immune privilege organ; factors, which affect cleavage and loading of antigenic peptides onto MHC class I and class II in hepatocytes and dendritic cells, and the modulating effects of ethanol and HCV on antigen presentation by liver cells. Altered antigen presentation in the liver limits the ability of the immune system to clear HCV and infected cells and contributes to disease progression. HCV by itself affects dendritic cell function, switching their cytokine profile to the suppressive phenotype of interleukin-10 (IL-10) and transforming growth factor beta (TGFβ) predominance, preventing cell maturation and allostimulation capacity. The synergistic action of ethanol with HCV results in the suppression of MHC class II-restricted antigen presentation. In addition, ethanol metabolism and HCV proteins reduce proteasome function and interferon signaling, thereby suppressing the generation of peptides for MHC class I-restricted antigen presentation. Collectively, ethanol exposure further impairs antigen presentation in HCV-infected liver cells, which may provide a partial explanation for exacerbations and the poor outcome of HCV infection in alcoholics.

Original languageEnglish (US)
Pages (from-to)1201-1208
Number of pages8
JournalWorld Journal of Gastroenterology
Volume15
Issue number10
DOIs
StatePublished - Mar 14 2009

Keywords

  • Alcohol
  • Antigen presentation
  • Hepatitis C Virus
  • Interferon alpha and gamma
  • Liver
  • MHC class
  • Major histocompatibility complex (MHC) class

ASJC Scopus subject areas

  • Gastroenterology

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