Cutting edge: Bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression
Cutting edge: Bacterial flagellin activates basolaterally expressed TLR5 to induce epithelial proinflammatory gene expression
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DOI：
10.4049/jimmunol.167.4.1882
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发表时间：
2001-08-15
影响因子：
4.4
通讯作者：
Madara, JL
中科院分区：
文献类型：
--
作者：
Gewirtz, AT;Navas, TA;Madara, JL
鞭毛蛋白是细菌鞭毛的结构成分，由致病菌和嗜热菌分泌。鞭毛蛋白激活肠上皮细胞促炎基因表达。然而，只有接触基底外侧上皮表面的鞭毛蛋白是促炎性的;顶端鞭毛蛋白没有影响。致病性沙门氏菌，而不是大肠杆菌，跨上皮移位鞭毛蛋白，从而激活上皮促炎基因的表达。研究上皮细胞如何检测鞭毛蛋白揭示了Toll样受体5（TLR 5）的细胞表面表达响应鞭毛蛋白赋予NF-κ B基因表达。这种应答依赖于细胞外富含亮氨酸的重复序列和细胞内TLR 5的Toll/IL-1 R同源区以及衔接蛋白MyD 88。此外，免疫定位和细胞表面选择性生物素化显示，TLR 5只在肠上皮细胞的基底外侧表面表达，从而为这种先天免疫反应的极性提供了分子基础。因此，通过基底外侧TLR 5检测鞭毛蛋白介导上皮驱动的对沙门氏菌的炎症反应。
Flagellin, the structural component of bacterial flagella, is secreted by pathogenic and commensal bacteria. Flagellin activates proinflammatory gene expression in intestinal epithelia. However, only flagellin that contacts basolateral epithelial surfaces is proinflammatory; apical flagellin has no effect. Pathogenic Salmonella, but not commensal Escherichia coli, translocate flagellin across epithelia, thus activating epithelial proinflammatory gene expression. Investigating how epithelia detect flagellin revealed that cell surface expression of Toll-like receptor 5 (TLR5) conferred NF-kappaB gene expression in response to flagellin. The response depended on both extracellular leucine-rich repeats and intracellular Toll/IL-1R homology region of TLR5 as well as the adaptor protein MyD88. Furthermore, immunolocalization and cell surface-selective biotinylation revealed that TLR5 is expressed exclusively on the basolateral surface of intestinal epithelia, thus providing a molecular basis for the polarity of this innate immune response. Thus, detection of flagellin by basolateral TLR5 mediates epithelial-driven inflammatory responses to Salmonella.