Serum bridging molecules drive candidal invasion of human but not mouse endothelial cells.

Autor: Quynh T Phan, Norma V Solis, Jianfeng Lin, Marc Swidergall, Shakti Singh, Hong Liu, Donald C Sheppard, Ashraf S Ibrahim, Aaron P Mitchell, Scott G Filler
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: PLoS Pathogens, Vol 18, Iss 7, p e1010681 (2022)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1010681
Popis: 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.
Databáze: Directory of Open Access Journals
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