Serum bridging molecules drive candidal invasion of human but not mouse endothelial cells.
Serum bridging molecules drive candidal invasion of human but not mouse endothelial cells.
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血清桥接分子驱动念珠菌对人内皮细胞的侵袭，而不是小鼠内皮细胞。
DOI：
10.1371/journal.ppat.1010681
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发表时间：
2022-07
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
作者：
在血源性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部组织。虽然形成菌丝的白色念珠菌容易侵入内皮细胞，但其他医学上重要的念珠菌属物种在标准体外测定中的侵入性较差，并且在播散性感染的免疫活性小鼠模型中具有低毒力。在这里，我们表明，光滑念珠菌，热带念珠菌，近平滑念珠菌，克柔念珠菌可以结合到玻连蛋白和高分子量激肽原存在于人血清中。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。小鼠内皮细胞对这种内皮细胞侵袭机制的支持较差，但当小鼠内皮细胞经工程改造表达人gC1qR或αv整联蛋白时，这种机制可以恢复。总之，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使用的常见致病策略。侵入人类血管内皮细胞血管内皮细胞的侵袭是血源性播散性念珠菌病发病的关键步骤。除了C.对白色念珠菌侵入内皮细胞的认识很少。在这里，我们证明光滑念珠菌和其他念珠菌属。利用血清蛋白激肽原和玻连蛋白作为真菌与宿主细胞之间的桥梁分子，粘附并侵入人内皮细胞。当与真菌表面结合时，这些血清蛋白与内皮细胞表面的球状C1q受体（gC1qR）和αv整联蛋白相互作用，诱导内吞作用。这一过程发生在人内皮细胞中，但不发生在小鼠内皮细胞中，但可以在表达人gC1qR或整合素αv的小鼠内皮细胞中恢复。因此，桥接分子介导的内吞作用是医学上重要的念珠菌属的常见机制。侵入人血管内皮细胞。
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 and have low virulence in immunocompetent mouse models of disseminated infection. 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. The invasion of vascular endothelial cells is a key step in the pathogenesis of hematogenously disseminated candidiasis. How species of Candida other than C. albicans invade endothelial cells is poorly understood. Here, we demonstrate that Candida glabrata and other Candida spp. adhere to and invade human endothelial cells by utilizing the serum proteins kininogen and vitronectin as bridging molecules between the fungus and the host cell. When bound to the surface of the fungi, these serum proteins interact with the globular C1q receptor (gC1qR) and αv integrins on the endothelial cell surface, inducing endocytosis. This process occurs with human but not mouse endothelial cells but can be restored in mouse endothelial cells that express human gC1qR or integrin αv. Thus, bridging molecule-mediated endocytosis is a common mechanism by which medically important Candida spp. invade human vascular endothelial cells.
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影响因子：
15.9
作者：
CHEUNG, AL;KRISHNAN, M;FISCHETTI, VA
通讯作者：
FISCHETTI, VA
影响因子：
64.5
作者：
Lo, HJ;Kohler, JR;Fink, GR
通讯作者：
Fink, GR
影响因子：
15.9
作者：
JAFFE, EA;NACHMAN, RL;MINICK, CR
通讯作者：
MINICK, CR
影响因子：
7.1
作者：
Cortegiani A;Misseri G;Fasciana T;Giammanco A;Giarratano A;Chowdhary A
通讯作者：
Chowdhary A
DOI：
10.1073/pnas.93.16.8552
发表时间：
1996-08-06
影响因子：
11.1
作者：
Joseph, K;Ghebrehiwet, B;Kaplan, AP
通讯作者：
Kaplan, AP