During hematogenously disseminated candidiasis, blood borne fungi must invade the endothelial cells that line the blood vessels to infect the deep tissues. Although Candida albicans, which forms hyphae, readily invades endothelial cells, other medically important species of Candida are poorly invasive in standard in vitro assays. Here, we show that Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei can bind to vitronectin and high molecular weight kininogen present in human serum. Acting as bridging molecules, vitronectin and kininogen bind to αv integrins and the globular C1q receptor (gC1qR), inducing human endothelial cells to endocytose the fungus. This mechanism of endothelial cell invasion is poorly supported by mouse endothelial cells, but can be restored when mouse endothelial cells are engineered to express human gC1qR or αv integrin. Overall, these data indicate that bridging molecule-mediated endocytosis is a common pathogenic strategy used by many medically important Candida spp. to invade human vascular endothelial cells.

中文翻译：

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鉴定介导念珠菌属物种对人内皮细胞侵袭的血清桥接分子

在血行播散性念珠菌病期间，血源性真菌必须侵入血管内皮细胞以感染深层组织。尽管形成菌丝的白色念珠菌很容易侵入内皮细胞，但其他医学上重要的念珠菌种类在标准体外测定中侵入性较差。在这里，我们展示了光滑念珠菌、热带念珠菌、近平滑念珠菌和克柔念珠菌可与人血清中存在的玻连蛋白和高分子量激肽原结合。作为桥接分子，玻连蛋白和激肽原与αv 整联蛋白和球状 C1q 受体 (gC1qR) 结合，诱导人内皮细胞内吞真菌。小鼠内皮细胞很少支持这种内皮细胞侵袭的机制，但当小鼠内皮细胞被设计为表达人 gC1qR 或 αv 整合素时，可以恢复。总的来说，这些数据表明桥接分子介导的内吞作用是许多医学上重要的念珠菌属常用的致病策略。侵入人体血管内皮细胞。