期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 198, 期 10, 页码 1563-1572出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20031220
关键词
inflammation; immunity; genetic predisposition to disease; genetic markers; bacterial infections
Although Toll-like receptors (TLRs) are critical mediators of the immune response to pathogens, the influence of polymorphisins 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 (TLK5(392STOP)) 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 TLR5(392STOP) increases human susceptibility to infection through an unusual dominant mechanism that compromises TLR-5's essential role as a regulator of the lung epithelial innate immune response.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据