Heterogeneity in lung macrophage control of Mycobacterium tuberculosis is determined by T cells.
Heterogeneity in lung macrophage control of Mycobacterium tuberculosis is determined by T cells.
复制标题
肺巨噬细胞控制结核分枝杆菌的异质性是由 T 细胞决定的。
DOI：
10.1101/2023.11.29.569283
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Behar,SamuelM
中科院分区：
文献类型：
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作者：
Lai,Rocky;Williams,Travis;Rakib,Tasfia;Lee,Jinhee;Behar,SamuelM
结核分枝杆菌感染后，肺泡巨噬细胞最初被感染，但不能有效地限制细菌复制。研究了M.肺中不同细胞类型之间的结核感染随着T细胞免疫的开始而改变，此时主要的感染细胞生态位从肺泡转移到单核细胞衍生的巨噬细胞（MDM）。我们假设不同细胞类型之间细菌分布的变化是由T细胞识别感染细胞及其随后激活抗菌效应机制的差异驱动的。我们发现，CD 4和CD 8 T细胞有效地消除M。它们在肺泡巨噬细胞中抑制结核感染，但在MDM中抑制感染的影响较小，这可能是细菌生态位。重要的是，CD 4 T细胞应答增强MDM向肺的募集。因此，感染的结果取决于T细胞亚群和受感染细胞之间的相互作用;两者都有助于感染的消退和持续。
Following Mycobacterium tuberculosis infection, alveolar macrophages are initially infected but ineffectively restrict bacterial replication. The distribution of M. tuberculosis among different cell types in the lung changes with the onset of T cell immunity when the dominant infected cellular niche shifts from alveolar to monocyte-derived macrophages (MDM). We hypothesize that changes in bacterial distribution among different cell types is driven by differences in T cell recognition of infected cells and their subsequent activation of antimicrobial effector mechanisms. We show that CD4 and CD8 T cells efficiently eliminate M. tuberculosis infection in alveolar macrophages, but they have less impact on suppressing infection in MDM, which may be a bacterial niche. Importantly, CD4 T cell responses enhance MDM recruitment to the lung. Thus, the outcome of infection depends on the interaction between the T cell subset and the infected cell; both contribute to the resolution and persistence of the infection.