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World J Gastroenterol. Mar 14, 2009; 15(10): 1201-1208
Published online Mar 14, 2009. doi: 10.3748/wjg.15.1201
Hepatitis C virus and ethanol alter antigen presentation in liver cells
Natalia A Osna
Natalia A Osna, Department of Internal Medicine, University of Nebraska Medical Center, Liver Study Unit R151, VA Medical Center, 4101 Woolworth Ave, Omaha, NE 68105, United States
Author contributions: This review was written by Osna NA.
Correspondence to: Natalia A Osna, MD, PhD, Department of Internal Medicine, University of Nebraska Medical Center, Liver Study Unit R151, VA Medical Center, 4101 Woolworth Ave, Omaha, NE 68105, United States. nosna@unmc.edu
Telephone: +1-402-9953735
Fax: +1-402-4490604
Received: December 17, 2008
Revised: January 14, 2009
Accepted: January 21, 2009
Published online: March 14, 2009
Abstract

Alcoholic patients have a high incidence of hepatitis C virus (HCV) 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.

Keywords: Alcohol, Antigen presentation, Hepatitis C Virus, Interferon alpha and gamma, Liver, Major histocompatibility complex (MHC) class I, MHC class II