Alcohol abuse enhances neuroinflammation and impairs immune responses in an animal model of human immunodeficiency virus-1 encephalitis
| Autor: | James Haorah, Anuja Ghorpade, Rindha Reddy, Bryan Knipe, Huanyu Dou, Yuri Persidsky, Jessica Leibhart, Jesse Chrastil, Raghava Potula, David Heilman |
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| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_treatment Lymphocyte Viremia HIV Infections Mice SCID Biology CD8-Positive T-Lymphocytes medicine.disease_cause Pathology and Forensic Medicine Mice Immune system Mice Inbred NOD medicine Animals Humans Encephalitis Viral Neuroinflammation Microglia Ethanol Macrophages Brain Immunosuppression medicine.disease Original Research Paper Alcoholism Disease Models Animal Oxidative Stress medicine.anatomical_structure Immunology HIV-1 Encephalitis Oxidative stress |
| Zdroj: | The American journal of pathology. 168(4) |
| ISSN: | 0002-9440 |
| Popis: | 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-gamma(+) T lymphocytes, a fivefold increase in viremia, and diminished expression of immunoproteasomes 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. |
| Databáze: | OpenAIRE |
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