In:
The Journal of Experimental Medicine, Rockefeller University Press, Vol. 198, No. 10 ( 2003-11-17), p. 1563-1572
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1540-9538
,
0022-1007
DOI:
10.1084/jem.20031220
Sprache:
Englisch
Verlag:
Rockefeller University Press
Publikationsdatum:
2003
ZDB Id:
1477240-1
