As HIV has fueled a global resurgence of tuberculosis over the last several decades, there is a growing awareness that HIV-mediated impairments in both innate and adaptive immunity contribute to the heightened risk of tuberculosis in people with HIV. Since early immune responses to Mycobacterium tuberculosis ( Mtb ) set the stage for subsequent control or progression to active tuberculosis disease, early host–pathogen interactions following Mtb infection can be thought of as establishing a mycobacterial “set point,” which we define as the mycobacterial burden at the point of adaptive immune activation. This early immune response is impaired in the context of HIV coinfection, allowing for a higher mycobacterial set point and greater likelihood of progression to active disease with greater bacterial burden. Alveolar macrophages, as the first cells to encounter Mtb in the lungs, play a critical role in containing Mtb growth and establishing the mycobacterial set point. However, a number of key macrophage functions, ranging from pathogen recognition and uptake to phagocytosis and microbial killing, are blunted in HIV coinfection. To date, research evaluating the effects of HIV on the alveolar macrophage response to Mtb has been relatively limited, particularly with regard to the critical early events that help to dictate the mycobacterial set point. A greater understanding of alveolar macrophage functions impacted by HIV coinfection will improve our understanding of protective immunity to Mtb and may reveal novel pathways amenable to intervention to improve both early immune control of Mtb and clinical outcomes for the millions of people worldwide infected with HIV.

中文翻译：

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HIV 和结核病“设定点”：HIV 如何损害肺泡巨噬细胞对结核病的反应并为疾病进展奠定基础

由于艾滋病毒在过去几十年中推动了全球结核病的复发，人们越来越意识到艾滋病毒介导的先天免疫和适应性免疫损伤会导致艾滋病毒感染者患结核病的风险增加。由于对结核分枝杆菌 ( Mtb ) 的早期免疫反应为随后控制或发展为活动性结核病疾病奠定了基础，因此 Mtb 感染后的早期宿主-病原体相互作用可以被认为是建立分枝杆菌“设定点”，我们将其定义为分枝杆菌适应性免疫激活点的负担。这种早期免疫反应在 HIV 合并感染的情况下会受到损害，从而导致更高的分枝杆菌设定点和更大的可能性发展为具有更大细菌负担的活动性疾病。肺泡巨噬细胞，作为第一个在肺中遇到 Mtb 的细胞，在抑制 Mtb 生长和建立分枝杆菌设定点方面发挥着关键作用。然而，许多关键的巨噬细胞功能，从病原体识别和摄取到吞噬作用和微生物杀死，在 HIV 合并感染中变得迟钝。迄今为止，评估 HIV 对 Mtb 的肺泡巨噬细胞反应影响的研究相对有限，特别是在有助于决定分枝杆菌设定点的关键早期事件方面。更好地了解受 HIV 合并感染影响的肺泡巨噬细胞功能将提高我们对 Mtb 保护性免疫的理解，并可能揭示适合干预的新途径，以改善 Mtb 的早期免疫控制和全球数百万人感染 HIV 的临床结果。