Open AccessGranulocyte Macrophage-Colony Stimulating Factor Reverses HIV Protein-Induced Mitochondrial Derangements in Alveolar Macrophages
Author(s) -
Bashar S. Staitieh,
Sara C. Auld,
Md Ahmed,
Xian Fan,
Natalia Smirnova,
Samantha M. Yeligar
Publication year - 2021
Publication title -
aids research and human retroviruses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.993
H-Index - 92
eISSN - 1931-8405
pISSN - 0889-2229
DOI - 10.1089/aid.2020.0176
Subject(s) - alveolar macrophage , macrophage , immunology , granulocyte macrophage colony stimulating factor , mitochondrion , biology , innate immune system , immune system , inflammation , receptor , cytokine , microbiology and biotechnology , biochemistry , in vitro
Despite the advent of antiretroviral therapy, people living with HIV suffer from a range of infectious and noninfectious 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. At an academic medical center, studies were completed on alveolar macrophages isolated from both wild-type and HIV transgenic (HIV Tg) rats and 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. GM-CSF receptor expression and mitochondrial function were impaired in macrophages isolated from HIV Tg rats, and treatment with GM-CSF restored GM-CSF receptor expression and mitochondrial function. GM-CSF treatment of HIV Tg 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 Tg rat model, impairments in mitochondrial bioenergetics were confirmed in alveolar macrophages isolated from human subjects with HIV. 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.