MyD88 is pivotal for the early inflammatory response and subsequent bacterial clearance and survival in a mouse model of Chlamydia pneumoniae pneumonia
MyD88 is pivotal for the early inflammatory response and subsequent bacterial clearance and survival in a mouse model of Chlamydia pneumoniae pneumonia
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DOI：
10.1074/jbc.m503225200
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发表时间：
2005-08-12
影响因子：
4.8
通讯作者：
Arditi, M
中科院分区：
文献类型：
--
作者：
Naiki, Y;Michelsen, KS;Arditi, M
肺炎衣原体是呼吸道感染和许多慢性病的病原体。在这里，我们研究了共同的TLR接头分子MyD88在宿主对肺炎衣原体诱导的小鼠肺炎反应中的作用。MyD88基因缺陷的小鼠对肺炎衣原体产生急性早期炎症反应的能力严重受损。尽管感染5天后肺部的细菌负荷与之相当，MyD88缺陷小鼠只表现出轻微的肺炎迹象，炎性介质的表达减少。MyD88缺陷小鼠不能上调促炎细胞因子和趋化因子，表现出CD8+和CD4+T细胞向肺部招募的延迟，并且在第14天无法清除肺部的病原体。在第14天，MyD88缺陷小鼠出现严重的慢性肺部炎症，IL-1β和干扰素-γ升高，导致死亡率增加，而野生型小鼠以及TLR2或TLR4缺陷小鼠从急性肺炎中恢复，没有表现出细菌清除延迟。因此，MyD88对于识别肺炎衣原体感染和启动针对这种微生物的快速有效的免疫宿主反应，从而清除受感染肺中的细菌是必不可少的。
Chlamydia pneumoniae is the causative agent of respiratory tract infections and a number of chronic diseases. Here we investigated the involvement of the common TLR adaptor molecule MyD88 in host responses to C. pneumoniae-induced pneumonia in mice. MyD88-deficient mice were severely impaired in their ability to mount an acute early inflammatory response toward C. pneumoniae. Although the bacterial burden in the lungs was comparable 5 days after infection, MyD88-deficient mice exhibited only minor signs of pneumonia and reduced expression of inflammatory mediators. MyD88-deficient mice were unable to up-regulate proinflammatory cytokines and chemokines, demonstrated delayed recruitment of CD8+ and CD4+ T cells to the lungs, and were unable to clear the pathogen from their lungs at day 14. At day 14 the MyD88-deficent mice developed a severe, chronic lung inflammation with elevated IL-1 beta and IFN-gamma leading to increased mortality, whereas wild-type mice as well as TLR2- or TLR4-deficient mice recovered from acute pneumonia and did not show delayed bacterial clearance. Thus, MyD88 is essential to recognize C. pneumoniae infection and initiate a prompt and effective immune host response against this organism leading to clearance of bacteria from infected lungs.