Alcohol abuse enhances neuroinflammation and impairs immune responses in an animal model of human immunodeficiency virus-1 encephalitis

Raghava Potula, James Haorah, Bryan Knipe, Jessica Leibhart, Jesse Chrastil, David Heilman, Huanyu Dou, Rindha Reddy, Anuja Ghorpade, Yuri Persidsky

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Neuroinflammatory disorders (including human immunodeficiency virus-1 encephalitis, HIVE) are associated with oxidative stress and inflammatory brain injury, and excessive alcohol use can exacerbate tissue damage. Using a murine model of HIVE, we investigated the effects of alcohol abuse on the clearance of virus-infected macrophages and neuroinflammation. Severe combined immunodeficient mice were reconstituted with human lymphocytes, and encephalitis was induced by intracranial injection of HIV-1-infected monocyte-derived macrophages (HIV-1+ MDM). Animals were fed an ethanol-containing diet beginning 2 weeks before lymphocyte engraftment and for the entire duration of the experiment Lymphocyte engraftment was not altered by ethanol exposure. Alcohol-mediated immunosuppression in ethanol-fed mice was manifested by a significant decrease in CD8+/interferon-γ+ T lymphocytes, a fivefold increase in viremia, and diminished expression of imnnunoproteasomes in the spleen. Although both groups showed similar amounts of CD8+ T-lymphocyte infiltration in brain areas containing HIV-1 + MDMs, ethanol-fed mice featured double the amounts of HIV-1 + MDMs in the brain compared to controls. Ethanol-exposed mice demonstrated higher microglial reaction and enhanced oxidative stress. Alcohol exposure impaired immune responses (increased viremia, decreased immunoproteasome levels, and prevented efficient elimination of HIV-1 + MDMs) and enhanced neuroinflammation in HIVE mice. Thus, alcohol abuse could be a co-factor in progression of HIV-1 infection of the brain.

Original languageEnglish
Pages (from-to)1335-1344
Number of pages10
JournalAmerican Journal of Pathology
Volume168
Issue number4
DOIs
StatePublished - Apr 2006

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