CD31（PECAM-1）是梭状芽胞杆菌β-毒素内皮细胞特异性受体。

CD31 (PECAM-1) Serves as the Endothelial Cell-Specific Receptor of Clostridium perfringens β-Toxin.

机构信息

Institute of Animal Pathology, Department of Infectious Diseases and Pathobiology, Vetsuisse-Faculty, University of Bern, 3012 Bern, Switzerland.

Department of Chemistry and Biochemistry, Faculty of Sciences, University of Bern, 3012 Bern, Switzerland.

出版信息

Cell Host Microbe. 2020 Jul 8;28(1):69-78.e6. doi: 10.1016/j.chom.2020.05.003. Epub 2020 Jun 3.

DOI:10.1016/j.chom.2020.05.003

PMID:32497498

Abstract

Clostridium perfringens β-toxin (CPB) is a highly active β-pore-forming toxin (β-PFT) and the essential virulence factor for fatal, necro-hemorrhagic enteritis in animals and humans. The molecular mechanisms involved in CPB's action on its target, the endothelium of small intestinal vessels, are poorly understood. Here, we identify platelet endothelial cell adhesion molecule-1 (CD31 or PECAM-1) as the specific membrane receptor for CPB on endothelial cells. CD31 expression corresponds with the cell-type specificity of CPB, and it is essential for toxicity in cultured cells and mice. Ectopic CD31 expression renders resistant cells and liposomes susceptible to CPB-induced membrane damage. Moreover, the extracellular Ig6 domain of mouse, human, and porcine CD31 is essential for the interaction with CPB. Hence, our results explain the cell-type specificity of CPB in vitro and in the natural disease caused by C. perfringens type C.

摘要

产气荚膜梭菌β 毒素（CPB）是一种具有高度活性的β 孔形成毒素（β-PFT），也是动物和人类致命性、坏死性出血性肠炎的必需毒力因子。CPB 作用于其靶标——小肠血管内皮细胞的分子机制尚不清楚。在这里，我们确定血小板内皮细胞黏附分子-1（CD31 或 PECAM-1）是内皮细胞上 CPB 的特异性膜受体。CD31 的表达与 CPB 的细胞类型特异性相对应，并且对于培养细胞和小鼠中的毒性是必需的。异位 CD31 表达使耐药细胞和脂质体易受 CPB 诱导的膜损伤。此外，小鼠、人类和猪 CD31 的细胞外 Ig6 结构域对于与 CPB 的相互作用是必需的。因此，我们的结果解释了 CPB 在体外和由 C. perfringens 型 C 引起的天然疾病中的细胞类型特异性。