Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
Cell Host Microbe. 2012 Sep 13;12(3):301-12. doi: 10.1016/j.chom.2012.07.009.
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.
中性粒细胞通常是宿主防御入侵病原体的第一道防线，它们通过氧化和非氧化机制来破坏病原体。然而，尽管人们早就认识到中性粒细胞在结核病发病部位的存在，但它们在抵御分枝杆菌方面的作用尚不清楚。在这里，我们利用斑马鱼的遗传可操作性和光学透明性来监测中性粒细胞在感染海洋分枝杆菌（一种天然的鱼类病原体）过程中的行为及其后果。与巨噬细胞不同，中性粒细胞在初始感染部位不会与分枝杆菌相互作用。随后，中性粒细胞被招募到新生肉芽肿中，以响应来自肉芽肿内死亡感染巨噬细胞的信号，吞噬它们。一些中性粒细胞随后通过 NADPH 氧化酶依赖的机制迅速杀死内化的分枝杆菌。我们的研究结果为观察到的人类结核肉芽肿中的中性粒细胞模式以及慢性肉芽肿病患者易感染分枝杆菌提供了一种机制联系。
