Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction.

Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction. Research Abstract Details 

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Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction. Abstract Text:

Costica Aloman,Stephan Gehring,Philip Wintermeyer,Noriyoshi Kuzushita,Jack R Wands,

BACKGROUND & AIMS: Alcoholic patients with and without chronic liver disease have a high incidence of infection with hepatitis C virus (HCV). Long-term ethanol consumption in mice has been associated with a strikingly reduced CD8(+) cytotoxic T-lymphocyte (CTL) response to HCV nonstructural proteins following DNA-based immunization. This study evaluated the effect of ethanol on dendritic cells (DCs) as a mechanism(s) for reduced CTL activity. METHODS: Mice were fed an ethanol-containing or isocaloric pair-fed control diet for 8 weeks, followed by DC isolation from the spleen. DCs were evaluated with respect to endocytosis properties, cell surface markers, allostimulatory activity, and cytokine production following stimulation. Immune responses to HCV NS5 protein were generated by genetic immunization. Syngeneic transfer was used to determine if DC dysfunction contributed to abnormal cellular immune responses. RESULTS: Long-term ethanol exposure resulted in a reduced number of splenic DCs but did not alter endocytosis capacity. There was an increase in the myeloid and a reduction in the lymphoid DC population. Ethanol reduced expression of CD40 and CD86 costimulatory molecules on resting DCs, which was corrected following stimulation with lipopolysaccharide or poly I:C. There was impaired allostimulatory activity. Cytokine profiles of DCs isolated from ethanol-fed mice were characterized by enhanced interleukin (IL)-1beta and IL-10 and decreased tumor necrosis factor alpha, IL-12, interferon gamma, and IL-6 secretion. Impaired CTL responses to NS5 were corrected by syngeneic transfer of control DCs. CONCLUSIONS: Altered DC function is one of the major changes induced by long-term ethanol consumption, which subsequently impairs the cellular immune response necessary for viral clearance.

Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction. Publishing Authors By Initials

C Aloman,S Gehring,P Wintermeyer,N Kuzushita,JR Wands,

For similar proteins: viral proteins: viral nonstructural proteins research abstracts see: proteins: viral proteins: viral nonstructural proteins research

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MEDLINE DATE:

Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Gastroenterology

VOLUME: 132

Page Numbers: 698-708

Journal Abbreviation: Gastroenterology

ISSN: 0016-5085

DAY: 10

MONTH: 11

YEAR: 2006

Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 374630

Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction. Keywords Mesh Terms:

KEYWORDS: Viral Nonstructural Proteins

MESH TERMS: immunology

Chemical & Substance for Abstract: Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction. Information

Substance Name: Ethanol

Registry Number: 64-17-5

Grant and Affiliation Information for Chronic ethanol consumption impairs cellular immune responses against HCV NS5 protein due to dendritic cell dysfunction.

AFFILIATION: Liver Research Center, Rhode Island Hospital and Brown Medical School, Providence, Rhode Island 02903, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA-35711

ACRONYM: CA

MEDLINETA: Gastroenterology

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