Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229; and.
Department of Microbiology and Immunology, University of Texas Health Science Center, San Antonio, TX 78229; and Center for Airway Inflammation Research, University of Texas Health Science Center, San Antonio, TX 78229.
J Immunol. 2014 Aug 1;193(3):1373-82. doi: 10.4049/jimmunol.1400145. Epub 2014 Jun 25.
How intestinal epithelial cells (IECs) recognize pathogens and activate inflammasomes at intestinal surfaces is poorly understood. We hypothesized that IECs use integrin receptors to recognize pathogens and initiate inflammation within the intestinal tract. We find that IECs infected with Yersinia enterocolitica, an enteric pathogen, use β1 integrins as pathogen recognition receptors detecting the bacterial adhesin invasin (Inv). The Inv-integrin interaction provides the first signal for NLRP3 inflammasome activation with the type three secretion system translocon providing the second signal for inflammasome activation, resulting in release of IL-18. During infection, Yersinia employs two virulence factors, YopE and YopH, to counteract Inv-mediated integrin-dependent inflammasome activation. Furthermore, NLRP3 inflammasome activation in epithelial cells requires components of the focal adhesion complex signaling pathway, focal adhesion kinase, and rac1. The binding of Inv to β1 integrins rapidly induces IL-18 mRNA expression, suggesting integrins provide a first signal for NLRP3 inflammasome activation. These data suggest integrins function as pathogen recognition receptors on IECs to rapidly induce inflammasome-derived IL-18-mediated responses.
肠上皮细胞 (IECs) 如何识别病原体并在肠道表面激活炎症小体尚不清楚。我们假设 IECs 使用整合素受体识别病原体并在肠道内引发炎症。我们发现，感染肠致病性耶尔森氏菌 (Yersinia enterocolitica) 的 IECs 将 β1 整合素用作识别细菌黏附素侵袭素 (Inv) 的病原体识别受体。Inv-整合素相互作用为 NLRP3 炎症小体激活提供了第一个信号，III 型分泌系统转位子提供了炎症小体激活的第二个信号，导致 IL-18 的释放。在感染过程中，耶尔森氏菌使用两种毒力因子 YopE 和 YopH 来对抗 Inv 介导的整合素依赖性炎症小体激活。此外，上皮细胞中 NLRP3 炎症小体的激活需要粘着斑复合物信号通路的成分、粘着斑激酶和 rac1。Inv 与 β1 整合素的结合迅速诱导 IL-18 mRNA 的表达，这表明整合素为 NLRP3 炎症小体的激活提供了第一个信号。这些数据表明整合素作为 IECs 上的病原体识别受体，可快速诱导炎症小体衍生的 IL-18 介导的反应。
