Flagellin is the major proinflammatory determinant of enteropathogenic Salmonella
Flagellin is the major proinflammatory determinant of enteropathogenic Salmonella
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DOI：
10.4049/jimmunol.171.7.3668
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发表时间：
2003-10-01
影响因子：
4.4
通讯作者：
Neish, AS
中科院分区：
文献类型：
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作者：
Zeng, H;Carlson, AQ;Neish, AS
引起胃肠炎的沙门氏菌引起肠道上皮细胞转录的深刻变化，导致中性粒细胞重新聚集，中性粒细胞的存在是沙门氏菌病的组织病理学特征。在这里，我们使用基因芯片表达谱来定义在模型肠上皮中介导这种变化的分子决定因素。肠源性沙门氏菌诱导典型的促炎基因表达程序，类似于典型的促炎激动剂肿瘤坏死因子-α激活的程序。非前炎性细菌，无论是共生菌(大肠杆菌)还是系统性病原体(伤寒沙门氏菌)，都不能激活这个表达谱。虽然缺乏SPI-1编码的III型系统的鼠伤寒沙门氏菌是完全促炎的，但缺乏鞭毛结构成分鞭毛蛋白基因的菌株几乎没有促炎信号。最后，通过添加纯化鞭毛蛋白可以在很大程度上重现上皮促炎反应。因此，鼠伤寒沙门氏菌鞭毛蛋白是该病原体激活肠道上皮促炎症基因表达的主要分子触发因子。
The gastroenteritis-causing pathogen Salmonella typhimurium induces profound transcriptional changes in intestinal epithelia resulting in the recruitment of neutrophils whose presence is the histopathologic hallmark of salmonellosis. Here we used cDNA microarray expression profiling to define the molecular determinants that mediate such changes in model intestinal epithelia. Enteropathogenic Salmonella induced a classical proinflammatory gene expression program similar to that activated by the canonical proinfiammatory agonist TNF-alpha. Nonproinfiammatory bacteria,both commensals (Escherichia coli) and systemic pathogens (S. typhi), did not activate this expression profile. While S. typhimurium strains lacking the SPI-1-encoded type III system were fully proinflammatory, strains lacking the genes for the flagellar structural component flagellin were nearly devoid of proinflammatory signaling. Lastly, the epithellial proinflammatory response could be largely recapitulated by basolateral addition of purified flagellin. Thus, S. typhimurium flagellin is the major molecular trigger by which this pathogen activates gut epithelial proinflammatory gene expression.