Neutrophils exert protection in the early tuberculous granuloma by oxidative killing of mycobacteria phagocytosed from infected macrophages.
Neutrophils exert protection in the early tuberculous granuloma by oxidative killing of mycobacteria phagocytosed from infected macrophages.
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DOI：
10.1016/j.chom.2012.07.009
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发表时间：
2012-09-13
影响因子：
30.3
通讯作者：
Ramakrishnan L
中科院分区：
文献类型：
--
作者：
Yang CT;Cambier CJ;Davis JM;Hall CJ;Crosier PS;Ramakrishnan L
中性粒细胞通常是宿主防御入侵病原体的第一反应者，它们通过氧化和非氧化机制破坏入侵病原体。然而，尽管长期以来人们认识到结核病发病部位存在中性粒细胞，但其在防御分枝杆菌中的作用尚不清楚。在这里，我们利用斑马鱼的遗传易处理性和光学透明度来监测中性粒细胞的行为及其在感染海洋分枝杆菌（一种天然鱼类病原体）期间的后果。与巨噬细胞相反，中性粒细胞在初始感染部位不与分枝杆菌相互作用。中性粒细胞随后响应于来自肉芽肿内死亡的感染巨噬细胞的信号而被募集到新生肉芽肿，它们吞噬这些信号。一些中性粒细胞通过NADPH氧化酶依赖性机制迅速杀死内化的分枝杆菌。我们的研究结果提供了一个机制联系到中性粒细胞在人类结核性肉芽肿和人类慢性肉芽肿病的易感性，分枝杆菌感染的观察模式。
Neutrophils are typically the first responders in host defense against invading pathogens, which they destroy by both oxidative and nonoxidative mechanisms. However, despite a longstanding recognition of neutrophil presence at disease sites in tuberculosis, their role in defense against mycobacteria is unclear. Here we exploit the genetic tractability and optical transparency of zebrafish to monitor neutrophil behavior and its consequences during infection with Mycobacterium marinum, a natural fish pathogen. In contrast to macrophages, neutrophils do not interact with mycobacteria at initial infection sites. Neutrophils are subsequently recruited to the nascent granuloma in response to signals from dying infected macrophages within the granuloma, which they phagocytose. Some neutrophils then rapidly kill the internalized mycobacteria through NADPH oxidase-dependent mechanisms. Our results provide a mechanistic link to the observed patterns of neutrophils in human tuberculous granulomas and the susceptibility of humans with chronic granulomatous disease to mycobacterial infection.
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影响因子：
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作者：
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