Clostridium difficile flagella predominantly activate TLR5-linked NF-κB pathway in epithelial cells
Clostridium difficile flagella predominantly activate TLR5-linked NF-κB pathway in epithelial cells
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DOI：
10.1016/j.anaerobe.2016.01.002
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发表时间：
2016-04-01
期刊：
影响因子：
2.3
通讯作者：
Kansau, Imad
中科院分区：
文献类型：
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作者：
Batah, Jameel;Deneve-Larrazet, Cecile;Kansau, Imad
艰难梭菌已成为导致肠道院内抗生素后感染的最常见肠道病原体。这与高毒力菌株出现相关的严重病例的出现同时发生。这些毒素是主要的毒力因子，在艰难梭菌感染期间引起炎症反应。然而，其他细菌成分似乎也参与了炎症过程。在某些病原体中，鞭毛通过异常刺激 TLR5 介导的宿主免疫反应在发病机制中发挥作用。迄今为止，很少有研究探讨艰难梭菌鞭毛的这一作用。在当前的研究中，我们在两种不同的上皮细胞模型中证实，艰难梭菌通过其 FliC 鞭毛蛋白与 TLR5 相互作用。此外，通过抑制和转录组学研究，我们证明鞭毛蛋白和 TLR5 的相互作用主要通过 TLR5 激活 NF-kappa B，并在较小程度上激活 MAPK 通路，导致促炎基因表达和促炎介质合成的上调。这些结果表明艰难梭菌鞭毛在宿主肠道细胞炎症反应中发挥着作用。 (C) 2016 Elsevier Ltd. 保留所有权利。
Clostridium difficile has become the most common enteropathogen responsible for intestinal nosocomial post-antibiotic infections. This has coincided with the appearance of serious cases related to the emergence of hypervirulent strains. The toxins are the main virulence factors and elicit an inflammatory response during C. difficile infection. However, other bacterial components appear to be involved in the inflammatory process. In some pathogens, flagella play a role in pathogenesis through abnormal stimulation of the TLR5-mediated host immune response. To date, few studies have addressed this role for C. difficile flagella. In the current study, we confirm in two different epithelial cell models that C. difficile thanks to its FliC flagellin interacts with TLR5. In addition, thanks to inhibition and transcriptomic studies we demonstrate that the interaction of flagellin and TLR5 predominantly activates the NF-kappa B and, in a lesser degree, the MAPK pathways, via TLR5, leading to up-regulation of pro-inflammatory gene expression and synthesis of pro-inflammatory mediators. These results suggest a role for C. difficile flagella in contributing to inflammatory response in host intestinal cells. (C) 2016 Elsevier Ltd. All rights reserved.