Costiniuk Cecilia T, Samarani Suzanne, Wang Lixing, Vigano MariaLuisa, Ahmad Ali
Programme en maladies infectieuses et immunité en santé mondiale, Institut de recherche du Centre universitaire de santé McGill, Montréal, QC, Canada, Département de Médecine expérimentale, Université McGill, Montréal QC, Canada.
Programme en maladies infectieuses et immunité en santé mondiale, Institut de recherche du Centre universitaire de santé McGill, Montréal, QC, Canada.
Virologie (Montrouge). 2024 Aug 1;28(4):255-276. doi: 10.1684/vir.2024.1057.
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 co-infections 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.
虽然抗逆转录病毒疗法（ART）彻底改变了人类免疫缺陷病毒（HIV）的管理方式，并使HIV感染者（PLWH）能够实现接近正常的预期寿命，但由于HIV储存库的存在，治愈HIV仍然难以实现。此外，与普通人群相比，PLWH承受着更高的多种疾病负担，包括感染性和非感染性肺部疾病，这可能是HIV储存库形成的结果。他们的肠道、淋巴结、大脑、睾丸和肺部是储存库的重要解剖部位。虽然CD4+ T细胞，尤其是记忆性CD4+ T细胞，是最具特征的细胞HIV储存库，但组织驻留巨噬细胞（TRM）和肺泡巨噬细胞（AM）也携带HIV感染。在健康状态下，AM是支气管肺泡灌洗液（BAL）中最丰富的细胞，通过巡逻和清除碎片、微生物以及回收表面活性剂，在肺泡空间中充当哨兵。源自胚胎的长寿组织驻留AM具有自我更新能力，无需外周单核细胞补充。与其他组织一样，肺部紧密的细胞间接触也为HIV感染的细胞间传播和储存库的建立提供了有利环境。由于肺部持续暴露于来自外部环境的抗原，这种情况导致促炎表型，使肺部免疫细胞耗尽和衰老——这是一个有利于HIV持续存在的环境。烟草和电子烟吸烟、肺部微生物群失调和呼吸道合并感染等因素进一步驱动抗原刺激和HIV复制。反过来，HIV复制又导致持续的炎症和克隆扩增。本文讨论了AM在HIV持续存在中的潜在作用。此外，还探讨了它们对肺部炎症和免疫失调的贡献，这反过来可能使PLWH尽管接受了ART仍易患慢性肺病。最后，讨论了消除HIV感染的AM的策略。
