TLR2 is mobilized into an apical lipid raft receptor complex to signal infection in airway epithelial cells

被引:173
作者
Soong, G
Reddy, B
Sokol, S
Adamo, R
Prince, A
机构
[1] Columbia Univ, Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA
[2] Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA
关键词
D O I
10.1172/JCI200420773
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Toll-like receptors (TLRs) mediate host responses to bacterial gene products. As the airway epithelium is potentially exposed to many diverse inhaled bacteria, TLRs involved in defense of the airways must be broadly responsive, available at the exposed apical surface of the cells, and highly regulated to prevent activation following trivial encounters with bacteria. We demonstrate that TLR2 is enriched in caveolin-1-associated lipid raft microdomains presented on the apical surface of airway epithelial cells after bacterial infection. These receptor complexes include myeloid differentiation protein (MyD88), interleukin-1 receptor-activated kinase-1, and TNF receptor-associated factor 6. The signaling capabilities of TLR2 are amplified through its association with the asialoganglioside gangliotetraosylceramide (Galbeta1,2GalNAcbeta1,4Galbeta1,4Glcbeta1,1Cer), which has receptor function itself for many pulmonary pathogens. Ligation of either TLR2 or asialoGM1 by ligands with specificity for either receptor, by Pseudomonas aeruginosa, or by Staphylococcus aureus stimulates IL-8 production through activation of NF-kappaB, as mediated by TLR2 and MyD88. Thus, TLR2 in association with asialo-glycolipids presented within the context of lipid rafts provides a broadly responsive signaling complex at the apical surfaces of airway cells to initiate the host response to potential bacterial infection.
引用
收藏
页码:1482 / 1489
页数:8
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