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早期肺泡巨噬细胞反应和依赖于 IL-1R 的 T 细胞启动决定了结核分枝杆菌菌株的传染性。

Early alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains.

机构信息

Center for Emerging Pathogens, Department of Medicine, Rutgers-New Jersey Medical School, Newark, NJ, USA.

Núcleo de Doenças Infecciosas, NDI/Universidade Federal do Espirito Santo-UFES, Vitoria, Brazil.

出版信息

Nat Commun. 2022 Feb 16;13(1):884. doi: 10.1038/s41467-022-28506-2.

DOI:10.1038/s41467-022-28506-2
PMID:35173157
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8850437/
Abstract

Mechanisms underlying variability in transmission of Mycobacterium tuberculosis strains remain undefined. By characterizing high and low transmission strains of M.tuberculosis in mice, we show here that high transmission M.tuberculosis strain induce rapid IL-1R-dependent alveolar macrophage migration from the alveolar space into the interstitium and that this action is key to subsequent temporal events of early dissemination of bacteria to the lymph nodes, Th1 priming, granulomatous response and bacterial control. In contrast, IL-1R-dependent alveolar macrophage migration and early dissemination of bacteria to lymph nodes is significantly impeded in infection with low transmission M.tuberculosis strain; these events promote the development of Th17 immunity, fostering neutrophilic inflammation and increased bacterial replication. Our results suggest that by inducing granulomas with the potential to develop into cavitary lesions that aids bacterial escape into the airways, high transmission M.tuberculosis strain is poised for greater transmissibility. These findings implicate bacterial heterogeneity as an important modifier of TB disease manifestations and transmission.

摘要

结核分枝杆菌菌株传播变异性的潜在机制仍未阐明。通过对小鼠中高传播和低传播结核分枝杆菌菌株进行特征描述，我们在此表明，高传播结核分枝杆菌菌株可诱导肺泡巨噬细胞快速从肺泡空间向间质迁移，这种作用是随后细菌向淋巴结早期传播、Th1 细胞的启动、肉芽肿反应和细菌控制的关键。相比之下，在感染低传播结核分枝杆菌菌株时，IL-1R 依赖性肺泡巨噬细胞迁移和细菌向淋巴结的早期传播受到显著阻碍；这些事件促进了 Th17 免疫的发展，促进了中性粒细胞炎症和细菌复制的增加。我们的结果表明，高传播结核分枝杆菌菌株通过诱导具有发展成空洞性病变潜力的肉芽肿，帮助细菌逃入气道，从而更有可能传播。这些发现表明细菌异质性是结核病临床表现和传播的一个重要调节因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/d6d2320beff0/41467_2022_28506_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/c78965157e23/41467_2022_28506_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/bbdd31f44e84/41467_2022_28506_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/7cfbf3170a90/41467_2022_28506_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/d6d2320beff0/41467_2022_28506_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/60e27e4a7927/41467_2022_28506_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/5e611bd13cdb/41467_2022_28506_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/ee8476cdb65e/41467_2022_28506_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/c78965157e23/41467_2022_28506_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/bbdd31f44e84/41467_2022_28506_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/7cfbf3170a90/41467_2022_28506_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1d7/8850437/d6d2320beff0/41467_2022_28506_Fig8_HTML.jpg

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