HIV alters immunometabolic phenotypes of alveolar macrophages during chronic alcohol consumption 2795

Abstract Description People with human immunodeficiency virus (PWH) who heavily consume alcohol have suppressed lung function and increased respiratory symptoms. Even with antiretroviral therapy, HIV increases the risk for respiratory infections in part due to impaired phagocytosis in ∼50% of lung macrophages, suggesting heterogeneity in lung macrophages’ immune response to bacterial infections. Chronic oxidative stress drives alveolar macrophage (AM) phagocytic impairment by altering their activation and metabolic phenotypes. Understanding how HIV and chronic ethanol (EtOH) consumption alters the immunometabolic phenotypes of monocyte-derived AMs (MoAMs) and tissue-resident AMs (RAMs) is imperative to developing therapies to target dysregulated lung macrophages. In this study, MoAMs and RAMs were isolated from adult HIV-1 transgenic (HIV Tg) rats and treated ± chronic EtOH (0.08%, 72h). In addition, MoAMs and RAMs were isolated from PWH or uninfected individuals. AMs from HIV Tg rats showed alternative/deactivated polarization state, suppressed mitochondrial bioenergetics via increased oxidative stress, and impaired Staphylococcus aureus engulfment and clearance. HIV’s detrimental effects on AMs were exacerbated by chronic EtOH exposure. MoAMs from PWH were pro-inflammatory with normal phagocytic function and RAMs from PWH were anti-inflammatory with impaired phagocytosis. Our data support targeting oxidative stress to improve lung immunity in PWH who misuse alcohol. Funding Sources Supported by NIAAA/NIH R01AA026086. Topic Categories Immune Mechanisms of Human Disease (HUM)