PDF(Pubmed)
Abstract：
FimH-mediated bacterial invasion and polymorphonuclear neutrophil (PMN) transmigration across human brain microvascular endothelial cells (HBMECs) are required for the pathogenesis of Escherichia coli meningitis. However, the underlying mechanism remains unclear. This study demonstrated that the TnphoA mutant (22A33) and FimH-knockout mutant (ΔFimH) of E coli strain E44, which resulted in inactivation of FimH, were less invasive and less effective in promoting PMN transmigration than their wild-type strain. FimH protein induced PMN transmigration, whereas calmodulin inhibitor significantly blocked this effect. Moreover, immunofluorescence and co-immunoprecipitation analysis indicated that colocalized CD48 and α7 nAChR formed a complex on the surface of HBMECs that is associated with increased cofilin dephosphorylation, which could be remarkably enhanced by FimH+ E44. Our study concluded that FimH-induced E coli K1 invasion and PMN migration across HBMECs may be mediated by the CD48-α7nAChR complex in lipid rafts of HBMEC via Ca2+ signaling and cofilin dephosphorylation.
摘要：
FimH介导的细菌侵袭和多形核中性粒细胞（PMN）跨人脑微血管内皮细胞（HBMECs）的迁移是大肠杆菌脑膜炎的发病机理所必需的。然而,潜在机制尚不清楚.这项研究表明，大肠杆菌菌株E44的TnphoA突变体（22A33）和FimH敲除突变体（ΔFimH）导致FimH失活，与野生型菌株相比，侵入性较小，在促进PMN迁移方面效果较差。FimH蛋白诱导PMN迁移,而钙调蛋白抑制剂显著阻断了这种作用。此外，免疫荧光和免疫共沉淀分析表明，共定位的CD48和α7nAChR在HBMECs表面形成了一个复合物，该复合物与cofilin去磷酸化增加有关，FimH+E44可以显着增强。我们的研究得出结论，FimH诱导的大肠杆菌K1侵袭和PMN跨HBMECs的迁移可能是由HBMEC脂筏中的CD48-α7nAChR复合物通过Ca2信号传导和cofilin去磷酸化介导的。
