Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria
Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria
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DOI：
10.1073/pnas.0605200103
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发表时间：
2006-08-15
影响因子：
11.1
通讯作者：
Alexopoulou, Lena
中科院分区：
文献类型：
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作者：
Feuillet, Vincent;Medjane, Samir;Alexopoulou, Lena
Toll样受体(Toll-like Receptor，TLRs)是免疫系统的关键组成部分，可以检测微生物感染并触发抗微生物宿主防御反应。TLR5是单体鞭毛蛋白的传感器，单体鞭毛蛋白是细菌鞭毛的一种成分，已知是一种毒力因子。在这项研究中，我们建立了TLR5缺陷小鼠，并研究了TLR5信号在检测鞭毛蛋白以及对鼠伤寒沙门氏菌和铜绿假单胞菌抗菌免疫反应中的作用。我们发现TLR5在体内和体外对细菌鞭毛蛋白的识别都是必不可少的。TLR5在抗菌宿主免疫应答中的作用感染鼠伤寒沙门氏菌或鼻腔给药铜绿假单胞菌可被TLR4或其他传感机制掩盖。通过使用放射骨髓嵌合体，我们证明了在ip。注射鞭毛的免疫反应是由淋巴样细胞介导的，而鼻腔注射鞭毛蛋白时需要常驻细胞来启动反应。这些结果表明，鞭毛在不同器官中的识别是由不同的表达TI-115的细胞介导的，并为天然免疫系统在识别细菌病原体中使用的TLR5和TLR4信号通路的合作提供了见解。
Toll-like receptors (TLRs) are key components of the immune system that detect microbial infection and trigger antimicrobial host defense responses. TLR5 is a sensor for monomeric flagellin, which is a component of bacterial flagella known to be a virulence factor. In this study we generated TLR5-deficient mice and investigated the role of TLR5 signaling in the detection of flagellin and antibacterial immune responses to Salmonella typhimuriurn and Pseudomonas aeruginosa. We found that TLR5 is essential for the recognition of bacterial flagellin both in vivo and ex vivo. TLR5 contribution to antibacterial host response to i.p. infection with S. typhimurium or intranasal administration of A aeruginosa may be masked by TLR4 or other sensing mechanisms. By using radiation bone marrow chimera, we showed that upon i.p. injection of flagellin immune responses are mediated by lymphoid cells, whereas resident cells are required for the initiation of response upon intranasal flagellin administration. These results suggest that flagellin recognition in different organs is mediated by distinct TI-115-expressing cells and provide insights into the cooperation of the TLR5 and TLR4 signaling pathways used by the innate immune system in the recognition of bacterial pathogens.