Dot/Icm-Dependent Restriction of Legionella pneumophila within Neutrophils.
Dot/Icm-Dependent Restriction of Legionella pneumophila within Neutrophils.
复制标题
DOI：
10.1128/mbio.01008-21
复制
发表时间：
2021-06-29
期刊：
影响因子：
6.4
通讯作者：
Kwaik YA
中科院分区：
文献类型：
--
作者：
Price CTD;Hanford HE;Vashishta A;Ozanic M;Santic M;Uriarte S;Kwaik YA
嗜肺军团菌的Dot/Icm IV型分泌系统（T4 SS）对于病原体的溶酶体逃避和巨噬细胞的细胞内增殖的容许性是必需的。相反，我们发现多形核细胞（PMNs）通过快速限制L.嗜肺菌具体地说，我们表明，L。嗜肺细胞T4 SS注射的淀粉酶（LamA）效应子催化PMN胞质溶胶中的快速糖原降解，导致胞质高葡萄糖。中性粒细胞通过免疫代谢重编程应答，包括上调有氧糖酵解。PMNs被激活，在含军团菌的吞噬体（LCP）内空间产生细胞内活性氧，并将特异性和嗜天青颗粒融合到LCP，导致快速限制L。嗜肺菌我们的结论是，在相反的巨噬细胞，中性粒细胞响应的功能点/ICM系统，特别是注射的淀粉酶效应的影响，通过快速参与主要的杀微生物过程和快速限制的病原体。
The Dot/Icm type IV secretion system (T4SS) of Legionella pneumophila is essential for lysosomal evasion and permissiveness of macrophages for intracellular proliferation of the pathogen. In contrast, we show that polymorphonuclear cells (PMNs) respond to a functional Dot/Icm system through rapid restriction of L. pneumophila. Specifically, we show that the L. pneumophila T4SS-injected amylase (LamA) effector catalyzes rapid glycogen degradation in the PMNs cytosol, leading to cytosolic hyperglucose. Neutrophils respond through immunometabolic reprogramming that includes upregulated aerobic glycolysis. The PMNs become activated with spatial generation of intracellular reactive oxygen species within the Legionella-containing phagosome (LCP) and fusion of specific and azurophilic granules to the LCP, leading to rapid restriction of L. pneumophila. We conclude that in contrast to macrophages, PMNs respond to a functional Dot/Icm system, and specifically to the effect of the injected amylase effector, through rapid engagement of major microbicidal processes and rapid restriction of the pathogen.