High susceptibility to respiratory Acinetobacter baumannii infection in A/J mice is associated with a delay in early pulmonary recruitment of neutrophils
High susceptibility to respiratory Acinetobacter baumannii infection in A/J mice is associated with a delay in early pulmonary recruitment of neutrophils
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DOI：
10.1016/j.micinf.2009.06.003
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发表时间：
2009-10-01
影响因子：
5.8
通讯作者：
Chen, Wangxue
中科院分区：
文献类型：
--
作者：
Qiu, Hongyu;KuoLee, Rhonda;Chen, Wangxue
鲍曼不动杆菌是社区相关性和医院性肺炎的重要原因，由于多种抗生素耐药性的迅速发展，这种肺炎越来越难以治疗。尽管具有重要的临床意义，但呼吸道鲍曼不动杆菌感染的发病机制和宿主防御机制在很大程度上仍然未知。为了研究可能有助于防御的宿主因素，我们比较了A/J和C57BL/6小鼠对鼻内接种鲍曼不动杆菌的敏感性。我们发现A/J小鼠比C57BU6小鼠更易感染，死亡率（P < 0.05）和组织细菌负荷（P < 0.01）高于C57BU6小鼠，肺和脾脏的组织病理学更大。更重要的是，A/J小鼠的高易感性与局部促炎细胞因子/趋化因子（特别是IL-1 β、MIP-2和tnf - α）反应降低以及中性粒细胞早期流入肺的显著延迟和减少有关（P < 0.05）。A/J小鼠鼻内给予中性粒细胞诱导趋化因子MIP-2可增强肺中性粒细胞内流，并部分恢复宿主对鲍曼不动杆菌的抗性，其水平与C57BU6小鼠相当。我们的研究结果表明，嗜中性粒细胞的早期募集进入肺部对于启动有效的宿主防御呼吸道鲍曼杆菌感染至关重要。英国皇家版权所有(C) 2009年Elsevier Masson SAS出版。所有航班预订。
Acinetobacter baumannii is an important cause of both community-associated and nosocomial pneumonia, which have become increasingly difficult to treat because of the rapid development of resistance to multiple antibiotics. Despite its clinical importance, the pathogenesis of and host defense against respiratory A. baumannii infection remains largely unknown. To examine host factors that could contribute to the defense, we compared the susceptibilities of A/J and C57BL/6 mice to intranasal (i.n.) inoculation with A. baumannii. We found that A/J mice were significantly more susceptible to infection with higher mortality (P < 0.05) and tissue bacterial burdens (P < 0.01) as well as greater histopathology in the lung and spleen than C57BU6 mice. More importantly, the high susceptibility of A/J mice was associated with a reduced local proinflammatory cytokine/chemokine (particularly IL-1 beta, MIP-2 and TNF-alpha) responses and a significant delay and reduction in the early influx of neutrophils in the lung (P < 0.05). Intranasal administration of neutrophil-inducing chemokine MIP-2 to A/J mice enhanced pulmonary neutrophil influx and partially restored host resistance to A. baumannii to a level comparable to the more resistant C57BU6 mice. Our results imply that the early recruitment of neutrophils into the lung is critical for initiating an efficient host defense against respiratory A. baumannii infection. Crown Copyright (C) 2009 Published by Elsevier Masson SAS. All fights reserved.