What is the role of nitric oxide in murine and human host defense against tuberculosis? Current knowledge
What is the role of nitric oxide in murine and human host defense against tuberculosis? Current knowledge
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DOI：
10.1165/ajrcmb.25.5.4487
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发表时间：
2001-11-01
影响因子：
6.4
通讯作者：
Schluger, NW
中科院分区：
文献类型：
--
作者：
Chan, ED;Chan, J;Schluger, NW
天然免疫细胞产生的活性氧中间体和活性氮中间体被认为是抵抗微生物病原体的有效宿主防御机制。在结核病(TB)小鼠模型中，一氧化氮(NO)在单核巨噬细胞对结核分枝杆菌的杀伤中起重要作用。例如，在带有诱导型一氧化氮合酶(iNOS-/-)基因中断的小鼠品系中，感染结核分枝杆菌与传播和死亡的风险显著增加有关。尽管在人类中更具争议性，但越来越多的证据表明，由结核感染的巨噬细胞和上皮细胞产生的NO也具有抗结核分枝杆菌的作用。NO和其他活性氮化合物拮抗结核分枝杆菌的确切机制(S)尚不清楚，但可能涉及破坏细菌DNA、蛋白质、信号和/或诱导含有分枝杆菌的巨噬细胞凋亡。除了肿瘤坏死因子-α和白介素1-β等细胞因子外，分枝杆菌细胞壁成分如阿拉伯甘露聚糖和19kD脂蛋白，以及T细胞来源的干扰素-γ也可能诱导不表达。以达尔文式的方式，似乎某些结核分枝杆菌菌株已经进化出对抗NO毒副作用的策略。
The production of reactive oxygen intermediates and reactive nitrogen intermediates by innate immune cells is considered to be an effective host-defense mechanism against microbial pathogens. In the murine model of tuberculosis (TB), nitric oxide (NO) plays an essential role in the killing of Mycobacterium tuberculosis by mononuclear phagocytes. For example, in the mouse strain with a genetic disruption for inducible NO synthase (iNOS-/-), infection with M. tuberculosis is associated with a significantly higher risk of dissemination and mortality. Although more controversial in humans, there is a growing body of evidence that NO produced by TB-infected macrophages and by epithelial cells also has antimycobacterial effects against M. tuberculosis. The precise mechanism(s) by which NO and other reactive nitrogen species antagonize M. tuberculosis is not known, but may involve disruption of bacterial DNA, proteins, signaling, and/or induction of apoptosis of macrophages that harbor mycobacteria. In addition to cytokines such as tumor necrosis factor-alpha and interleukin 1-beta, mycobacterial cell wall components such as lipoarabinomannan and 19 kD lipoprotein, along with the T-cell-derived interferon-gamma, may also induce NO expression. In a Darwinian fashion, it also appears that certain strains of M. tuberculosis have evolved strategies to combat the toxic effects of NO.