Focal Area Infection Biology, University of Basel, 4056 Basel, Switzerland.
FACS Core Facility, University of Basel, 4056 Basel, Switzerland.
Cell Host Microbe. 2014 Jan 15;15(1):72-83. doi: 10.1016/j.chom.2013.12.006.
Reactive oxygen and nitrogen species function in host defense via mechanisms that remain controversial. Pathogens might encounter varying levels of these species, but bulk measurements cannot resolve such heterogeneity. We used single-cell approaches to determine the impact of oxidative and nitrosative stresses on individual Salmonella during early infection in mouse spleen. Salmonella encounter and respond to both stresses, but the levels and impact vary widely. Neutrophils and inflammatory monocytes kill Salmonella by generating overwhelming oxidative stress through NADPH oxidase and myeloperoxidase. This controls Salmonella within inflammatory lesions but does not prevent their spread to more permissive resident red pulp macrophages, which generate only sublethal oxidative bursts. Regional host expression of inducible nitric oxide synthase exposes some Salmonella to nitrosative stress, triggering effective local Salmonella detoxification through nitric oxide denitrosylase. Thus, reactive oxygen and nitrogen species influence dramatically different outcomes of disparate Salmonella-host cell encounters, which together determine overall disease progression.
活性氧和氮物种通过仍存在争议的机制在宿主防御中发挥作用。病原体可能会遇到不同水平的这些物质，但总体测量无法解决这种异质性。我们使用单细胞方法来确定氧化应激和硝化应激对感染早期小鼠脾脏中单个沙门氏菌的影响。沙门氏菌会遇到并对这两种应激作出反应，但水平和影响差异很大。中性粒细胞和炎症性单核细胞通过 NADPH 氧化酶和髓过氧化物酶产生压倒性的氧化应激来杀死沙门氏菌。这可以控制炎症病变内的沙门氏菌，但不能阻止它们传播到更允许的常驻红髓巨噬细胞，这些巨噬细胞仅产生亚致死性氧化爆发。诱导型一氧化氮合酶在宿主中的区域表达使一些沙门氏菌暴露于硝化应激下，通过一氧化氮脱硝化酶引发有效的局部沙门氏菌解毒作用。因此，活性氧和氮物种显著影响不同沙门氏菌-宿主细胞接触的不同结果，这些结果共同决定了整体疾病进展。
