Yersinia enterocolitica exploits different pathways to accomplish adhesion and toxin injection into host cells
Yersinia enterocolitica exploits different pathways to accomplish adhesion and toxin injection into host cells
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DOI：
10.1111/cmi.12429
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发表时间：
2015-08
影响因子：
3.4
通讯作者：
B. Keller;M. Mühlenkamp;E. Deuschle;A. Siegfried;S. Mössner;Jessica Schade;Tanja Griesinger;N. Katava;C. Braunsdorf;B. Fehrenbacher;L. Jiménez-Soto;M. Schaller;R. Haas;H. Genth;S. Retta;Hannelore Meyer;R. Böttcher;R. Zent;M. Schütz;I. Autenrieth;E. Bohn
中科院分区：
文献类型：
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作者：
B. Keller;M. Mühlenkamp;E. Deuschle;A. Siegfried;S. Mössner;Jessica Schade;Tanja Griesinger;N. Katava;C. Braunsdorf;B. Fehrenbacher;L. Jiménez-Soto;M. Schaller;R. Haas;H. Genth;S. Retta;Hannelore Meyer;R. Böttcher;R. Zent;M. Schütz;I. Autenrieth;E. Bohn
目前的范例表明，小肠结肠炎耶尔森氏菌（Ye）通过外膜蛋白耶尔森氏菌粘附素A（YadA）或侵袭素（Inv）粘附到宿主细胞，以促进III型分泌系统注射Yops。在该过程中，Inv直接结合宿主细胞的β1整联蛋白，而YadA可以通过细胞外基质蛋白间接结合β1整联蛋白。在这里，我们挑战了这种范式，并研究了Yop注入的要求。我们证明了Inv介导的粘附而不是YadA介导的粘附取决于β1整合素的结合和激活，并且紧密粘附是Yop注射的先决条件。通过新型转基因细胞系、shRNA方法和RGD肽，我们发现YadA与Inv相反，可以使用广泛的宿主细胞受体库进行宿主细胞粘附。在不存在β1整联蛋白的情况下，YadA通过与αV整联蛋白相互作用以及上皮细胞（而不是成纤维细胞）表达的未知辅因子协同作用来介导Yop注射。电子显微镜和流动室研究表明，Yop注射需要Ye和宿主细胞之间的限定的紧密接触区域，从而产生抵抗剪切应力的粘附力。因此，YadA与不同细胞类型的广泛的细胞外基质（ECM）结合宿主细胞受体库的间接结合使得YadA成为确保Yop注射的通用工具。总之，考虑到在Ye感染过程中外膜蛋白Inv和YadA的差异表达以及各种宿主细胞群体的整合素的差异表达，数据表明Ye灵活地装备以在不同的宿主细胞类型中完成Yop注射，这是其免疫逃避策略中的中心事件。
The current paradigm suggests that Yersinia enterocolitica (Ye) adheres to host cells via the outer membrane proteins Yersinia adhesin A (YadA) or invasin (Inv) to facilitate injection of Yops by the type III secretion system. In this process Inv binds directly to β1 integrins of host cells while YadA may bind indirectly via extracellular matrix proteins to β1 integrins. Here we challenged this paradigm and investigated the requirements for Yop injection. We demonstrate that Inv‐ but not YadA‐mediated adhesion depends on β1 integrin binding and activation, and that tight adhesion is a prerequisite for Yop injection. By means of novel transgenic cell lines, shRNA approaches and RGD peptides, we found that YadA, in contrast to Inv, may use a broad host cell receptor repertoire for host cell adhesion. In the absence of β1 integrins, YadA mediates Yop injection by interaction with αV integrins in cooperation with yet unknown cofactors expressed by epithelial cells, but not fibroblasts. Electron microscopic and flow chamber studies revealed that a defined intimate contact area between Ye and host cells resulting in adhesion forces resisting shear stress is required for Yop injection. Thus, the indirect binding of YadA to a broad extracellular matrix (ECM) binding host cell receptor repertoire of different cell types makes YadA a versatile tool to ensure Yop injection. In conclusion, given the differential expression of the outer membrane proteins Inv and YadA in the course of Ye infection and differential expression of integrins by various host cell populations, the data demonstrate that Ye is flexibly armed to accomplish Yop injection in different host cell types, a central event in its immune evasion strategy.