Division of Pulmonary, Critical Care & Sleep, Department of Internal Medicine, University of 0Nebraska Medical Center, Omaha, NE, USA.
VA Nebraska Western Iowa Health Care System, Omaha, NE, USA.
Results Probl Cell Differ. 2024;73:537-549. doi: 10.1007/978-3-031-62036-2_21.
Pneumonia, as well as other types of acute and chronic lung injuries, remain the leading causes of death in individuals living with HIV. Individuals with HIV who are on antiretroviral therapy continue to have a greater risk for pneumonia, including bacterial and mycobacterial infections. Alveolar macrophages and lung epithelial cells constitute the first line of host defense against invading pathogens. The predisposition of individuals living with HIV to infections despite ante-retroviral therapy is mechanistically related to HIV pro-viruses integrating into host cells, including airway epithelial cells and alveolar macrophages. Alveolar macrophages harbor latent HIV even when individuals appear to have complete suppression on ART. In parallel, pneumonia can irreversibly impair lung function in HIV-infected individuals. Cells that Macrophages exposed to HIV or HIV-related proteins have been shown to secrete exosomes that contain miRNAs. These exosomes can regulate several innate and acquired immune functions by stimulating cytokine production and inflammatory responses. Furthermore, these secreted exosomal miRNAs can shuttle between cells, causing cellular dysfunction in the case of epithelial cells; they disrupt lung epithelial barrier dysfunction, which leads to a predisposition to bacterial infections. We discuss the common bacterial infections that occur in patients living with HIV and provide mechanistic insights into how the intercellular communication of miRNAs results in cellular dysfunction.
肺炎以及其他类型的急性和慢性肺损伤仍然是 HIV 感染者死亡的主要原因。接受抗逆转录病毒治疗的 HIV 感染者仍然面临更大的肺炎风险,包括细菌和分枝杆菌感染。肺泡巨噬细胞和肺上皮细胞构成了宿主防御入侵病原体的第一道防线。尽管接受了抗逆转录病毒治疗,HIV 感染者仍然容易感染,其机制与 HIV 前病毒整合到宿主细胞有关,包括气道上皮细胞和肺泡巨噬细胞。即使在接受 ART 治疗的个体中 HIV 似乎完全受到抑制,肺泡巨噬细胞仍携带潜伏的 HIV。同时,肺炎可使 HIV 感染者的肺功能不可逆转地受损。已经表明,暴露于 HIV 或与 HIV 相关蛋白的巨噬细胞会分泌含有 miRNA 的外泌体。这些外泌体可以通过刺激细胞因子产生和炎症反应来调节几种先天和获得性免疫功能。此外,这些分泌的外泌体 miRNA 可以在细胞之间穿梭,导致上皮细胞的细胞功能障碍;它们破坏肺上皮细胞屏障功能,导致易发生细菌感染。我们讨论了 HIV 感染者中常见的细菌感染,并提供了有关 miRNA 细胞间通讯如何导致细胞功能障碍的机制见解。