NADPH-oxidase but not inducible nitric oxide synthase contributes to resistance in a murine Staphylococcus aureus Newman pneumonia model
NADPH-oxidase but not inducible nitric oxide synthase contributes to resistance in a murine Staphylococcus aureus Newman pneumonia model
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DOI：
10.1016/j.micinf.2011.05.004
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发表时间：
2011-10-01
影响因子：
5.8
通讯作者：
Steinmetz, Ivo
中科院分区：
文献类型：
--
作者：
Koehler, Jens;Breitbach, Katrin;Steinmetz, Ivo
金黄色葡萄球菌是一种经常导致包括肺炎在内的严重医院感染的病原体。本研究的目的是研究先天性吞噬细胞介导的免疫机制，使用先前描述的小鼠S。金黄色纽曼肺炎模型。我们发现，BALB/c小鼠代表了一个更敏感的小鼠品系相比，C57 BL/6小鼠鼻内S。金黄色葡萄球菌纽曼挑战。消耗实验表明，中性粒细胞是抵抗的关键决定因素，而消耗肺泡巨噬细胞在一定程度上保护小鼠免受急性肺S。金黄色葡萄球菌攻击。缺乏NADPH氧化酶亚基gp 9 lphox的C57 BL/6小鼠（gp 9 lphox-/-小鼠）被证明对病原体高度易感。相反，C57 BL/6诱导型一氧化氮合酶缺陷（iNOS-/-）小鼠感染后的临床结果没有差异。iNOS-/-和gp 9 lphox-/-小鼠的骨髓巨噬细胞在控制S.金黄色的我们的数据表明，中性粒细胞和NADPH氧化酶介导的机制是保护宿主免受肺S。金黄色葡萄球菌纽曼挑战。相反，巨噬细胞以及NO介导的机制似乎并没有发挥关键作用的阻力在这个模型中。(C)2011年巴斯德研究所。出版社：Elsevier Masson SAS All rights reserved.
Staphylococcus aureus is a pathogen that often causes severe nosocomial infections including pneumonia. The present study was designed to examine innate phagocyte mediated immune mechanisms using a previously described murine S. aureus Newman pneumonia model. We found that BALB/c mice represent a more susceptible mouse strain compared to C57BL/6 mice after intranasal S. aureus Newman challenge. Depletion experiments revealed that neutrophils are a crucial determinant for resistance whereas depletion of alveolar macrophages protected mice to some degree from acute pulmonary S. aureus challenge. C57BL/6 mice lacking the subunit gp9lphox of the NADPH-oxidase (gp9lphox-/- mice) proved to be highly susceptible against the pathogen. In contrast, C57BL/6 inducible nitric oxidase synthase deficient (iNOS-/-) mice did not differ in their clinical outcome after infection. Neither bone marrow macrophages from iNOS-/- nor from gp9lphox-/- mice were impaired in controlling intracellular persistence of S. aureus. Our data suggest that neutrophil and NADPH-oxidase mediated mechanisms are essential components in protecting the host against pulmonary S. aureus Newman challenge. On contrary, macrophages as well as NO mediated mechanisms do not seem to play a critical role for resistance in this model. (C) 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.