Mechanisms of Candida albicans trafficking to the brain.
Mechanisms of Candida albicans trafficking to the brain.
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DOI：
10.1371/journal.ppat.1002305
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发表时间：
2011-10
期刊：
影响因子：
6.7
通讯作者：
Filler SG
中科院分区：
文献类型：
--
作者：
Liu Y;Mittal R;Solis NV;Prasadarao NV;Filler SG
在血行播散性疾病期间，白色念珠菌感染大多数器官，包括大脑。我们发现白色念珠菌 vps51Δ/Δ 突变体在播散性疾病小鼠模型中显着增加了对大脑的向性。为了研究这种增强向大脑运输的机制，我们在体外研究了野生型白色念珠菌和 vps51Δ/Δ 突变体与脑微血管内皮细胞的相互作用。这些研究表明，白色念珠菌对脑内皮细胞的入侵是由真菌入侵素 Als3 和 Ssa1 介导的。 Als3 与 gp96 热休克蛋白结合，该蛋白在脑内皮细胞表面表达，但不在人脐静脉内皮细胞表面表达，而 Ssa1 与 gp96 以外的脑内皮细胞受体结合。 vps51Δ/Δ突变体增加了Als3的表面表达，这是该突变体在体外侵入脑内皮细胞和运输至小鼠大脑的能力增加的主要原因。因此，在播散性疾病期间，白色念珠菌通过与 gp96（一种在脑内皮细胞表面特异性表达的独特受体）结合而运输到大脑并感染大脑。在血行播散性感染期间，真菌白色念珠菌通过血流传播到身体的几乎所有器官，包括大脑。大脑白色念珠菌感染是患有播散性念珠菌病的早产儿的一个重要问题。为了感染大脑，白色念珠菌必须粘附并侵入脑血管内皮细胞。这些内皮细胞在其表面表达独特的蛋白质，而其他血管床的内皮细胞不表达这些蛋白质。在这里，我们发现白色念珠菌通过与 gp96 结合来感染大脑，gp96 是一种在脑内皮细胞表面独特表达的热休克蛋白。 Gp96 与白色念珠菌 Als3 侵入素结合，诱导脑内皮细胞摄取该生物体。白色念珠菌 Ssa1 入侵素还介导脑内皮细胞对真菌的摄取，但它是通过与 gp96 以外的受体结合来实现的。因此，在血行播散性感染期间，白色念珠菌通过与 gp96（一种在脑内皮细胞表面特异性表达的受体）结合而运输至大脑并感染大脑。
During hematogenously disseminated disease, Candida albicans infects most organs, including the brain. We discovered that a C. albicans vps51Δ/Δ mutant had significantly increased tropism for the brain in the mouse model of disseminated disease. To investigate the mechanisms of this enhanced trafficking to the brain, we studied the interactions of wild-type C. albicans and the vps51Δ/Δ mutant with brain microvascular endothelial cells in vitro. These studies revealed that C. albicans invasion of brain endothelial cells is mediated by the fungal invasins, Als3 and Ssa1. Als3 binds to the gp96 heat shock protein, which is expressed on the surface of brain endothelial cells, but not human umbilical vein endothelial cells, whereas Ssa1 binds to a brain endothelial cell receptor other than gp96. The vps51Δ/Δ mutant has increased surface expression of Als3, which is a major cause of the increased capacity of this mutant to both invade brain endothelial cells in vitro and traffic to the brain in mice. Therefore, during disseminated disease, C. albicans traffics to and infects the brain by binding to gp96, a unique receptor that is expressed specifically on the surface of brain endothelial cells. During hematogenously disseminated infection, the fungus Candida albicans is carried by the bloodstream to virtually all organs in the body, including the brain. C. albicans infection of the brain is a significant problem in premature infants with disseminated candidiasis. To infect the brain, C. albicans must adhere to and invade the endothelial cells that line cerebral blood vessels. These endothelial cells express unique proteins on their surface that are not expressed by endothelial cells of other vascular beds. Here, we show that C. albicans infects the brain by binding to gp96, a heat shock protein that is uniquely expressed on the surface of brain endothelial cells. Gp96 is bound by the C. albicans Als3 invasin, which induces the uptake of this organism by brain endothelial cells. The C. albicans Ssa1 invasin also mediates fungal uptake by brain endothelial cells, but does so by binding to a receptor other than gp96. Thus, during hematogenously disseminated infection, C. albicans traffics to and infects the brain by binding to gp96, a receptor that is expressed specifically on the surface of brain endothelial cells.
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影响因子：
11.8
作者：
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