自噬
结核分枝杆菌
肺结核
CD11c公司
巨噬细胞
微生物学
病毒学
生物
髓样
免疫学
体外
医学
基因
细胞凋亡
表型
遗传学
病理
作者
Siwei Feng,Michael D. Connolly,Rachel L. Kinsella,Chanchal Sur Chowdhury,Sthefany M. Chavez,Sumanta Kumar Naik,Samuel R. McKee,Jacob A. Van Winkle,Neha Dubey,Amanda N. Samuels,Amanda Swain,Xiaoyan Cui,Skyler V. Hendrix,Reilly Woodson,Darren Kreamalmeyer,Asya Smirnov,Maxim N. Artyomov,Herbert W. Virgin,Yating Wang,Christina L. Stallings
出处
期刊:Nature microbiology
日期:2024-02-27
卷期号:9 (3): 684-697
被引量:2
标识
DOI:10.1038/s41564-024-01608-x
摘要
Although autophagy sequesters Mycobacterium tuberculosis (Mtb) in in vitro cultured macrophages, loss of autophagy in macrophages in vivo does not result in susceptibility to a standard low-dose Mtb infection until late during infection, leaving open questions regarding the protective role of autophagy during Mtb infection. Here we report that loss of autophagy in lung macrophages and dendritic cells results in acute susceptibility of mice to high-dose Mtb infection, a model mimicking active tuberculosis. Rather than observing a role for autophagy in controlling Mtb replication in macrophages, we find that autophagy suppresses macrophage responses to Mtb that otherwise result in accumulation of myeloid-derived suppressor cells and subsequent defects in T cell responses. Our finding that the pathogen-plus-susceptibility gene interaction is dependent on dose has important implications both for understanding how Mtb infections in humans lead to a spectrum of outcomes and for the potential use of autophagy modulators in clinical medicine. Autophagy in CD11c+ phagocytes prevents myeloid-derived suppressor cell recruitment and promotes protective T cell responses during high-dose Mycobacterium tuberculosis infection in mice.
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