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.

中文翻译：

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粒细胞巨噬细胞集落刺激因子逆转 HIV 蛋白诱导的肺泡巨噬细胞线粒体紊乱

尽管出现了抗逆转录病毒疗法，但 HIV 感染者仍患有一系列感染性和非感染性肺部并发症。HIV 通过减少粒细胞巨噬细胞集落刺激因子 (GM-CSF) 信号传导损害肺泡巨噬细胞的抗氧化防御和先天免疫功能。由于 GM-CSF 可能与线粒体有关，我们试图确定 HIV 对 GM-CSF 受体表达和肺泡巨噬细胞线粒体功能的影响。在一个学术医疗中心，对从野生型和 HIV 转基因 (HIV Tg) 大鼠以及感染和未感染 HIV 的人类受试者中分离出的肺泡巨噬细胞进行了研究。在存在和不存在 GM-CSF 治疗的情况下，对原代巨噬细胞进行电镀和评估 GM-CSF 受体 β、吞噬指数和线粒体功能的表达。从 HIV Tg 大鼠分离的巨噬细胞中 GM-CSF 受体表达和线粒体功能受损，用 GM-CSF 治疗恢复了 GM-CSF 受体表达和线粒体功能。HIV Tg 大鼠的 GM-CSF 治疗还增加了线粒体蛋白电压依赖性阴离子选择性通道 1 (VDAC) 和葡萄糖调节蛋白 75 (Grp75) 的肺泡巨噬细胞水平。与 HIV Tg 大鼠模型相似，线粒体生物能量学的损伤在从 HIV 感染者中分离出来的肺泡巨噬细胞中得到证实。肺泡巨噬细胞线粒体生物能量学中与 HIV 相关的损伤可能导致 HIV 感染中的先天免疫功能障碍，而 GM-CSF 治疗可能为减轻这些有害影响提供一种新的治疗策略。