Expression of the nitric oxide synthase 2 gene is not essential for early control of Mycobacterium tuberculosis in the murine lung
Expression of the nitric oxide synthase 2 gene is not essential for early control of Mycobacterium tuberculosis in the murine lung
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DOI：
10.1128/iai.68.12.6879-6882.2000
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发表时间：
2000-12-01
影响因子：
3.1
通讯作者：
Orme, IM
中科院分区：
文献类型：
--
作者：
Cooper, AM;Pearl, JE;Orme, IM
巨噬细胞活化的白细胞介素-12和γ干扰素（IFN-γ）途径在控制结核病中起着关键作用。在鼠模型中，通过诱导一氧化氮合酶2（NOS 2）基因产物产生补充性一氧化氮被认为是IFN-γ激活的巨噬细胞的主要抗菌机制。使用低剂量的气溶胶介导的感染模型，在小鼠中，我们研究了一氧化氮在控制肺结核分枝杆菌的作用。与全身性感染的后果相反，将法定剂量的细菌直接引入缺乏NOS 2基因的小鼠的肺部，几乎与完整动物一样受到控制。这与缺乏IFN-γ或IFN信号通路的关键成员干扰素调节因子1的小鼠中疾病的快速进展形成对比。因此，虽然IFN-γ在肺中细菌生长的早期控制中是关键的，但这种控制并不完全依赖于NOS 2基因的表达。然而，肺部缺乏诱导型一氧化氮确实会导致缺乏NOS 2基因的感染小鼠的肺部肉芽肿中多形核细胞参与增加并最终坏死。
The interleukin-12 and gamma interferon (IFN-gamma) pathway of macrophage activation plays a pivotal role in controlling tuberculosis. In the murine model, the generation of supplementary nitric oxide by the induction of the nitric oxide synthase 2 (NOS2) gene product is considered the principal antimicrobial mechanism of IFN-gamma -activated macrophages. Using a low-dose aerosol-mediated infection model in the mouse, we have investigated the role of nitric oxide in controlling Mycobacterium tuberculosis in the lung. In contrast to the consequences of a systemic infection, a law dose of bacteria introduced directly into the lungs of mice lacking the NOS2 gene is controlled almost as well as in intact animals. This is in contrast to the rapid progression of disease in mice lacking IFN-gamma or a key member of the IFN signaling pathway, interferon regulatory factor 1. Thus while IFN-gamma is pivotal in early control of bacterial growth in the lung, this control does not completely depend upon the expression of the NOS2 gene. The absence of inducible nitric oxide in the lung does, however, result in increased polymorphonuclear cell involvement and eventual necrosis in the pulmonary granulomas of the infected mice lacking the NOS2 gene.