Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. II. Effects on microbial proliferation and host survival in vivo.
Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. II. Effects on microbial proliferation and host survival in vivo.
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DOI：
10.1084/jem.192.2.237
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发表时间：
2000-07-17
影响因子：
15.3
通讯作者：
Dougan, G
中科院分区：
文献类型：
--
作者：
Mastroeni, P;Vazquez-Torres, A;Fang, F C;Xu, Y;Khan, S;Hormaeche, C E;Dougan, G
在gp 91 phox −/−、iNOS −/−和同源野生型小鼠中研究了NADPH吞噬细胞氧化酶（phox）和诱导型一氧化氮合酶（iNOS）在宿主对强毒鼠伤寒沙门氏菌的抗性中的作用。尽管gp 91 phox −/−和iNOS −/−小鼠对S.与野生型小鼠相比，gp 91 phox −/−和iNOS −/−小鼠品系中细菌复制的动力学显著不同。早在感染的第1天，与C57 BL/6对照组相比，gp 91 phox −/−小鼠的脾脏和肝脏中存在更多的细菌数量，并且所有gp 91 phox −/−小鼠在5天内死于感染。相比之下，只有在感染的第一周之后，在iNOS −/−小鼠的网状内皮器官中才检测到细菌负荷增加。在iNOS −/−小鼠中，炎性CD 11b+细胞的流入、肉芽肿形成和血清干扰素γ水平均未受损，但iNOS缺陷型肉芽肿无法限制细菌复制。NADPH吞噬细胞氧化酶和iNOS都是宿主对野生型沙门氏菌的抗性所必需的，但似乎主要在感染的不同阶段起作用。
The roles of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (iNOS) in host resistance to virulent Salmonella typhimurium were investigated in gp91phox −/−, iNOS −/−, and congenic wild-type mice. Although both gp91phox −/− and iNOS −/− mice demonstrated increased susceptibility to infection with S. typhimurium compared with wild-type mice, the kinetics of bacterial replication were dramatically different in the gp91phox −/− and iNOS −/− mouse strains. Greater bacterial numbers were present in the spleens and livers of gp91phox −/− mice compared with C57BL/6 controls as early as day 1 of infection, and all of the gp91phox −/− mice succumbed to infection within 5 d. In contrast, an increased bacterial burden was detected within reticuloendothelial organs of iNOS −/− mice only beyond the first week of infection. Influx of inflammatory CD11b+ cells, granuloma formation, and serum interferon γ levels were unimpaired in iNOS −/− mice, but the iNOS-deficient granulomas were unable to limit bacterial replication. The NADPH phagocye oxidase and iNOS are both required for host resistance to wild-type Salmonella, but appear to operate principally at different stages of infection.