Granulocyte Macrophage-Colony Stimulating Factor Reverses HIV Protein-Induced Mitochondrial Derangements in Alveolar Macrophages
- 1 March 2021
- journal article
- research article
- Published by Mary Ann Liebert Inc in AIDS Research and Human Retroviruses
- Vol. 37 (3), 224-232
- https://doi.org/10.1089/aid.2020.0176
Abstract
Background: Despite the advent of anti-retroviral therapy, people living with HIV suffer from a range of infectious and non-infectious pulmonary complications. HIV impairs antioxidant defenses and innate immune function of the alveolar macrophage by diminishing granulocyte macrophage-colony stimulating factor (GM-CSF) signaling. Since GM-CSF may be linked to mitochondria, we sought to determine the effects of HIV on GM-CSF receptor expression and alveolar macrophage mitochondrial function. Setting: Academic medical center Methods: Studies were completed on alveolar macrophages isolated from both wild-type and HIV transgenic rats as well as human subjects with and without HIV. Primary macrophages were plated and evaluated for expression of GM-CSF receptor beta, phagocytic index, and mitochondrial function in the presence and absence of GM-CSF treatment. Results: GM-CSF receptor expression and mitochondrial function were impaired in macrophages isolated from HIV transgenic rats, and treatment with GM-CSF restored GM-CSF receptor expression and mitochondrial function. GM-CSF treatment of HIV transgenic rats also increased alveolar macrophage levels of the mitochondrial proteins voltage-dependent anion-selective channel 1 (VDAC) and glucose-regulated protein 75 (Grp75). Similar to the HIV transgenic rat model, impairments in mitochondrial bioenergetics were confirmed in alveolar macrophages isolated from human subjects with HIV. Conclusion: HIV-associated impairments in alveolar macrophage mitochondrial bioenergetics likely contribute to innate immune dysfunction in HIV infection, and GM-CSF treatment may offer a novel therapeutic strategy for mitigating these deleterious effects.Keywords
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