Transient loss of resistance to pulmonary tuberculosis in p47phox-/- mice
Transient loss of resistance to pulmonary tuberculosis in p47phox-/- mice
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DOI：
10.1128/iai.68.3.1231-1234.2000
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发表时间：
2000-03-01
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;Segal, BH;Orme, IM
结核分枝杆菌是一种重要的呼吸道病原体，其生长主要由嘌呤激活的巨噬细胞控制。这种控制的主要介质之一是一氧化氮;然而，超氧化物最近已被证明是系统性分枝杆菌感染的保护。为了确定超氧化物是否在控制M。在原发性肺感染期间，缺乏胞质p47（phox）基因（其对于通过NADPH氧化酶有效产生超氧化物是必需的）的小鼠被产气感染。在M.结核病导致在感染的早期细菌生长显著增加。然而，一旦在引流淋巴结中检测到抗原特异性γ干扰素产生淋巴细胞，肺中的细菌生长就停止了。缺乏超氧化物的一个有趣的结果是肉芽肿内嗜中性粒细胞浸润增加，这可能是由于细菌生长更快导致组织损伤增加的结果，也可能反映了超氧化物在控制炎症中的作用。
Mycobacterium tuberculosis is an important respiratory pathogen the growth of which is controlled primarily by cytokine-activated macrophages. One of the principal mediators of this control is nitric oxide; however, superoxide has recently been shown to be protective in systemic mycobacterial infections. To determine whether superoxide is important in controlling M. tuberculosis during primary pulmonary infection, mice lacking the cytosolic p47(phox) gene (which is essential for effective superoxide production by the NADPH oxidase) were infected aerogenically. The lack of superoxide during an aerosol infection with M. tuberculosis resulted in a significant increase in bacterial growth over the early period of infection. Once antigen-specific gamma interferon-producing lymphocytes were detected in the draining lymph nodes, however, bacterial growth in the lung stopped. One interesting consequence of the lack of superoxide was an increase in neutrophilic infiltrates within the granuloma, This may be a consequence of increased tissue damage due to more rapid bacterial growth or may reflect a role for superoxide in controlling inflammation.