A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease.
A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease.
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一种常见的主导TLR5停止密码子多态性废除了鞭毛蛋白信号传导，并与对军团疾病的易感性有关。
DOI：
10.1084/jem.20031220
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发表时间：
2003-11-17
影响因子：
15.3
通讯作者：
Aderem, A
中科院分区：
文献类型：
--
作者：
Hawn, TR;Verbon, A;Lettinga, KD;Zhao, LP;Li, SS;Laws, RJ;Skerrett, SJ;Beutler, B;Schroeder, L;Nachman, A;Ozinsky, A;Smith, KD;Aderem, A
尽管Toll样受体（TLR）是对病原体的免疫应答的关键介质，但该基因家族中的多态性对人类感染易感性的影响知之甚少。我们最近证明TLR5识别鞭毛蛋白，鞭毛蛋白是一种存在于许多细菌鞭毛结构中的强效炎症刺激物。在这里，我们表明，TLR5（TLR5392STOP）的配体结合结构域中的共同终止密码子多态性无法介导鞭毛蛋白信号传导，以显性方式起作用，并与嗜肺军团菌（一种鞭毛细菌）引起的肺炎易感性相关。我们还表明，鞭毛蛋白是一个主要的刺激物的促炎细胞因子的生产在肺上皮细胞。总之，这些观察结果表明，TLR5392STOP通过一种不寻常的显性机制增加了人类对感染的易感性，该机制损害了TLR5作为肺上皮先天免疫应答调节剂的重要作用。
Although Toll-like receptors (TLRs) are critical mediators of the immune response to pathogens, the influence of polymorphisms in this gene family on human susceptibility to infection is poorly understood. We demonstrated recently that TLR5 recognizes flagellin, a potent inflammatory stimulus present in the flagellar structure of many bacteria. Here, we show that a common stop codon polymorphism in the ligand-binding domain of TLR5 (TLR5392STOP) is unable to mediate flagellin signaling, acts in a dominant fashion, and is associated with susceptibility to pneumonia caused by Legionella pneumophila, a flagellated bacterium. We also show that flagellin is a principal stimulant of proinflammatory cytokine production in lung epithelial cells. Together, these observations suggest that TLR5392STOP increases human susceptibility to infection through an unusual dominant mechanism that compromises TLR5's essential role as a regulator of the lung epithelial innate immune response.
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影响因子：
32.4
作者：
Kawai, T;Adachi, O;Akira, S
通讯作者：
Akira, S
影响因子：
6.4
作者：
Boshuizen, HC;Neppelenbroek, SE;Conyn-van Spaendonck, MAE
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Conyn-van Spaendonck, MAE
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作者：
Den Boer, JW;Yzerman, EPF;Conyn-Van Spaendonck, MAE
通讯作者：
Conyn-Van Spaendonck, MAE