Naiki Yoshikazu, Michelsen Kathrin S, Schröder Nicolas W J, Alsabeh Randa, Slepenkin Anatoly, Zhang Wenxuan, Chen Shuang, Wei Bo, Bulut Yonca, Wong Michelle H, Peterson Ellena M, Arditi Moshe
Division of Pediatrics Infectious Diseases and Immunology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA 90048, USA.
J Biol Chem. 2005 Aug 12;280(32):29242-9. doi: 10.1074/jbc.M503225200. Epub 2005 Jun 17.
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-1beta 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.
肺炎衣原体是呼吸道感染及多种慢性疾病的病原体。在此，我们研究了常见的Toll样受体（TLR）接头分子髓样分化因子88（MyD88）在小鼠宿主对肺炎衣原体诱导的肺炎反应中的作用。MyD88缺陷型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。尽管感染后5天肺部的细菌载量相当，但MyD88缺陷型小鼠仅表现出轻微的肺炎症状且炎症介质表达降低。MyD88缺陷型小鼠无法上调促炎细胞因子和趋化因子，肺中CD8⁺和CD4⁺T细胞的募集延迟，且在第14天时无法从肺中清除病原体。在第14天，MyD88缺陷型小鼠出现严重的慢性肺部炎症，白细胞介素-1β（IL-1β）和γ干扰素（IFN-γ）升高，导致死亡率增加，而野生型小鼠以及TLR2或TLR4缺陷型小鼠从急性肺炎中恢复，且未出现细菌清除延迟的情况。因此，MyD88对于识别肺炎衣原体感染并启动针对该病原体的迅速有效的免疫宿主反应从而从感染的肺部清除细菌至关重要。
