Key Points HIV infection is associated with the loss of CD163+CD206+ AM. Smoking increases surface expression of several activation markers on AM. CyTOF is a valuable tool for evaluating the phenotypic profile of BALF from smokers. HIV type 1 is associated with pulmonary dysfunction that is exacerbated by cigarette smoke. Alveolar macrophages (AM) are the most prominent immune cell in the alveolar space. These cells play an important role in clearing inhaled pathogens and regulating the inflammatory environment; however, how HIV infection impacts AM phenotype and function is not well understood, in part because of their autofluorescence and the absence of well-defined surface markers. The main aim of this study was to evaluate the impact of HIV infection on human AM and to compare the effect of smoking on their phenotype and function. Time-of-flight mass cytometry and RNA sequencing were used to characterize macrophages from human bronchoalveolar lavage of HIV-infected and -uninfected smokers and nonsmokers. We found that the frequency of CD163+ anti-inflammatory AM was decreased, whereas CD163−CCR7+ proinflammatory AM were increased in HIV infection. HIV-mediated proinflammatory polarization was associated with increased levels of inflammatory cytokines and macrophage activation. Conversely, smoking heightened the inflammatory response evident by change in the expression of CXCR4 and TLR4. Altogether, these findings suggest that HIV infection, along with cigarette smoke, favors a proinflammatory macrophage phenotype associated with enhanced expression of inflammatory molecules. Further, this study highlights time-of-flight mass cytometry as a reliable method for immunophenotyping the highly autofluorescent cells present in the bronchoalveolar lavage of cigarette smokers.

中文翻译：

---

HIV感染与抗炎肺泡巨噬细胞的损失有关

要点 HIV 感染与 CD163+CD206+ AM 的丢失有关。吸烟会增加 AM 上几种激活标记的表面表达。CyTOF 是评估吸烟者 BALF 表型特征的宝贵工具。HIV 1 型与因吸烟而加剧的肺功能障碍有关。肺泡巨噬细胞 (AM) 是肺泡空间中最突出的免疫细胞。这些细胞在清除吸入的病原体和调节炎症环境中发挥着重要作用；然而，HIV 感染如何影响 AM 表型和功能尚不清楚，部分原因是它们的自发荧光和缺乏明确定义的表面标志物。本研究的主要目的是评估 HIV 感染对人类 AM 的影响，并比较吸烟对其表型和功能的影响。飞行时间质谱流式细胞术和 RNA 测序用于表征来自 HIV 感染和未感染的吸烟者和非吸烟者的人类支气管肺泡灌洗液中的巨噬细胞。我们发现 CD163+ 抗炎性 AM 的频率降低，而 CD163-CCR7+ 促炎性 AM 在 HIV 感染中增加。HIV 介导的促炎极化与炎性细胞因子水平升高和巨噬细胞活化有关。相反，吸烟通过改变 CXCR4 和 TLR4 的表达来增强炎症反应。总而言之，这些发现表明 HIV 感染以及香烟烟雾有利于与炎症分子表达增强相关的促炎巨噬细胞表型。进一步，