Inhibition of antigen-presenting cell functions by alcohol: Implications for hepatitis C virus infection

G. Szabó, Angela Dolganiuc, Pranoti Mandrekar, Bernadette White

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The mechanisms of alcohol-induced immunosuppression include detects in innate and adaptive immune responses. Monocytes and dendritic cells (DCs) link innate and adaptive immune responses as they recognize viral antigens and induce antigen-specific T-cell activation. We investigated the effects of alcohol on antigen-presenting cell functions. Acute alcohol consumption by healthy volunteers (vodka, 2 ml/kg) resulted in significantly reduced antigen-presenting cell function of monocyte-derived DCs. Reduced allostimulatory capacity of DCs treated with alcohol in vitro correlated with decreased co-stimulatory molecule (B7.1 and B7.2) expression, as well as with reduced interleukin (IL)-12 and increased IL-10 concentrations, in mixed lymphocyte cultures. Dendritic cells recognize viral antigens in hepatitis C virus (HCV) infection, and HCV disease is accelerated in alcohol-dependent individuals. For patients with chronic HCV infection, we found reduced allostimulatory capacity of myeloid DCs. Furthermore, DC function was reduced by in vitro alcohol treatment of DCs obtained from HCV-infected patients, supporting the suggestion that viral factors and alcohol may interact to doubly suppress DC functions. We found that induction of maturation with lipopolysaccharide could not fully ameliorate the reduced DC allostimulatory capacity caused by alcohol treatment, HCV infection, or their combination. In addition, soluble factors in the supematants obtained from mixed lymphocyte cultures containing alcohol-treated DCs or DCs obtained from HCV-infected patients could transfer inhibition of T-cell proliferation in cultures containing DCs obtained from healthy volunteers. Anti-IL-10 neutralizing antibody ameliorated the reduced mixed lymphocyte reaction containing DCs obtained from HCV-infected patients, whereas exogenous IL-12, but not anti-IL-10, treatment ameliorated the reduced T-cell proliferation induced by alcohol treatment of DCs obtained from healthy volunteers. Our results support the suggestion that both acute alcohol intake and in vitro alcohol treatment inhibit DC antigen-presenting cell function and support the hypothesis that viral factors interact with alcohol to reduce DC functions in HCV infection.

Original languageEnglish
Pages (from-to)241-249
Number of pages9
JournalAlcohol
Volume33
Issue number3
DOIs
Publication statusPublished - 2004

Fingerprint

Antigen-Presenting Cells
Virus Diseases
Viruses
Hepacivirus
Dendritic Cells
contagious disease
alcohol
Alcohols
T-cells
Lymphocytes
Cell culture
Interleukin-10
Healthy Volunteers
proliferation
Inhibition (Psychology)
Viral Antigens
Cell proliferation
Adaptive Immunity
Interleukin-12
Innate Immunity

Keywords

  • Antigen presentation
  • Chronic HCV infection
  • Dendritic cells
  • Innate immunity
  • Monocytes
  • T-cell proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)
  • Behavioral Neuroscience
  • Neuroscience(all)
  • Toxicology
  • Health(social science)

Cite this

Inhibition of antigen-presenting cell functions by alcohol : Implications for hepatitis C virus infection. / Szabó, G.; Dolganiuc, Angela; Mandrekar, Pranoti; White, Bernadette.

In: Alcohol, Vol. 33, No. 3, 2004, p. 241-249.

Research output: Contribution to journalArticle

Szabó, G. ; Dolganiuc, Angela ; Mandrekar, Pranoti ; White, Bernadette. / Inhibition of antigen-presenting cell functions by alcohol : Implications for hepatitis C virus infection. In: Alcohol. 2004 ; Vol. 33, No. 3. pp. 241-249.
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AB - The mechanisms of alcohol-induced immunosuppression include detects in innate and adaptive immune responses. Monocytes and dendritic cells (DCs) link innate and adaptive immune responses as they recognize viral antigens and induce antigen-specific T-cell activation. We investigated the effects of alcohol on antigen-presenting cell functions. Acute alcohol consumption by healthy volunteers (vodka, 2 ml/kg) resulted in significantly reduced antigen-presenting cell function of monocyte-derived DCs. Reduced allostimulatory capacity of DCs treated with alcohol in vitro correlated with decreased co-stimulatory molecule (B7.1 and B7.2) expression, as well as with reduced interleukin (IL)-12 and increased IL-10 concentrations, in mixed lymphocyte cultures. Dendritic cells recognize viral antigens in hepatitis C virus (HCV) infection, and HCV disease is accelerated in alcohol-dependent individuals. For patients with chronic HCV infection, we found reduced allostimulatory capacity of myeloid DCs. Furthermore, DC function was reduced by in vitro alcohol treatment of DCs obtained from HCV-infected patients, supporting the suggestion that viral factors and alcohol may interact to doubly suppress DC functions. We found that induction of maturation with lipopolysaccharide could not fully ameliorate the reduced DC allostimulatory capacity caused by alcohol treatment, HCV infection, or their combination. In addition, soluble factors in the supematants obtained from mixed lymphocyte cultures containing alcohol-treated DCs or DCs obtained from HCV-infected patients could transfer inhibition of T-cell proliferation in cultures containing DCs obtained from healthy volunteers. Anti-IL-10 neutralizing antibody ameliorated the reduced mixed lymphocyte reaction containing DCs obtained from HCV-infected patients, whereas exogenous IL-12, but not anti-IL-10, treatment ameliorated the reduced T-cell proliferation induced by alcohol treatment of DCs obtained from healthy volunteers. Our results support the suggestion that both acute alcohol intake and in vitro alcohol treatment inhibit DC antigen-presenting cell function and support the hypothesis that viral factors interact with alcohol to reduce DC functions in HCV infection.

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