尽管抗逆转录病毒疗法(ART)彻底改变了人类免疫缺陷病毒(HIV)的管理,并使HIV感染者(PLWH)能够达到接近正常的预期寿命,由于艾滋病毒储库的存在,艾滋病毒的治愈仍然难以捉摸。此外,与普通人群相比,PLWH支持更高的多患病率负担,包括感染性和非感染性的肺部疾病,这可能是艾滋病毒储库形成的结果。他们的直觉,淋巴结,大脑,睾丸和肺是水库的重要解剖部位。而CD4+T细胞,特别是记忆CD4+T细胞,是特征最好的细胞HIV储库,组织驻留巨噬细胞(TRM)和肺泡巨噬细胞(AM)也有HIV感染。在健康条件下,AM是支气管肺泡(BAL)液中最丰富的细胞,并通过巡逻和清理碎片在肺泡空间充当哨兵,微生物和表面活性剂回收。胚胎起源的长寿命组织驻留AM具有自我更新的能力,无需从外周单核细胞补充。和其他组织一样,肺中紧密的细胞-细胞接触也提供了有利于HIV感染的细胞间传播和建立贮库的环境。由于肺部不断暴露于来自外部环境的抗原,这种情况有助于促炎表型,使肺免疫细胞耗尽和衰老-一种促进HIV持续存在的环境.吸烟和电子烟等因素,肺微生物群系失调和呼吸道共感染进一步驱动抗原刺激和HIV复制.HIV复制,反过来,有助于持续的炎症和克隆扩张。在这里,讨论了AM在HIV持续存在中的潜在作用.此外,它们对肺部炎症和免疫失调的贡献,这可能反过来使PLWH易患慢性肺病,尽管艺术,正在探索。最后,讨论了消除HIV感染的AM的策略。
While antiretroviral therapy (ART) has revolutionized the management of human immunodeficiency virus (HIV) and has enabled people living with HIV (PLWH) to achieve near-normal life expectancies, an HIV cure remains elusive due to the presence of HIV reservoirs. Furthermore, compared with individuals in the general population, PLWH support a higher burden of multimorbidity, including pulmonary diseases of both an infectious and non-infection nature, which may be a consequence of the formation of HIV reservoirs. Their gut, lymph nodes, brain, testes and lungs constitute important anatomic sites for the reservoirs. While CD4+ T cells, and particularly memory CD4+ T cells, are the best characterized cellular HIV reservoirs, tissue resident macrophages (TRM) and alveolar macrophages (AM) also harbor HIV infection. AM are the most abundant cells in bronchoalveolar (BAL) fluid in healthy conditions, and act as sentinels in the alveolar space by patrolling and clearing debris, microbes and surfactant recycling. Long-lived tissue-resident AM of embryonic origin have the capacity of self-renewal without replenishment from peripheral monocytes. As in other tissues, close cell-cell contacts in lungs also provide a milieu conducive for cell-to-cell spread of HIV infection and establishment of reservoirs. As lungs are in constant exposure to antigens from the external environment, this situation contributes to pro-inflammatory phenotype rendering pulmonary immune cells exhausted and senescent-an environment facilitating HIV persistence. Factors such as tobacco and e-cigarette smoking, lung microbiome dysbiosis and respiratory coinfections further drive antigenic stimulation and HIV replication. HIV replication, in turn, contributes to ongoing inflammation and clonal expansion. Herein, the potential role of AM in HIV persistence is discussed. Furthermore, their contribution towards pulmonary inflammation and immune dysregulation, which may in turn render PLWH susceptible to chronic lung disease, despite ART, is explored. Finally, strategies to eliminate HIV-infected AM are discussed.