Candida albicans is a common opportunistic fungal pathogen that causes a wide range of infections from superficial mucosal to hematogenously disseminated candidiasis. The hyphal form plays an important role in the pathogenic process by invading epithelial cells and causing tissue damage. Notably, the secretion of the hyphal toxin candidalysin is essential for both epithelial cell damage and activation of mucosal immune responses. However, the mechanism of candidalysin-induced cell death remains unclear. Here, we examined the induction of cell death by candidalysin in oral epithelial cells. Fluorescent imaging using healthy/apoptotic/necrotic cell markers revealed that candidalysin causes a rapid and marked increase in the population of necrotic rather than apoptotic cells in a concentration dependent manner. Activation of a necrosis-like pathway was confirmed since C. albicans and candidalysin failed to activate caspase-8 and -3, or the cleavage of poly (ADP-ribose) polymerase. Furthermore, oral epithelial cells treated with candidalysin showed rapid production of reactive oxygen species, disruption of mitochondria activity and mitochondrial membrane potential, ATP depletion and cytochrome c release. Collectively, these data demonstrate that oral epithelial cells respond to the secreted fungal toxin candidalysin by triggering numerous cellular stress responses that induce necrotic death.

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念珠菌溶血素触发诱导坏死性死亡的上皮细胞应激

白色念珠菌是一种常见的机会性真菌病原体，可引起从浅表黏膜到血行播散性念珠菌病的广泛感染。菌丝形式通过侵入上皮细胞并引起组织损伤在致病过程中起重要作用。值得注意的是，菌丝毒素念珠菌溶素的分泌对于上皮细胞损伤和粘膜免疫反应的激活都是必不可少的。然而，念珠菌溶素诱导的细胞死亡的机制仍不清楚。在这里，我们检查了念珠菌溶素在口腔上皮细胞中对细胞死亡的诱导作用。使用健康/凋亡/坏死细胞标记物的荧光成像显示，念珠菌溶血素以浓度依赖性方式导致坏死而不是凋亡细胞的数量快速且显着增加。白色念珠菌和假丝酵母菌素未能激活 caspase-8 和 -3，或聚 (ADP-核糖) 聚合酶的裂解。此外，用念珠菌溶素处理的口腔上皮细胞表现出快速产生活性氧、破坏线粒体活性和线粒体膜电位、ATP 耗竭和细胞色素 c 释放。总的来说，这些数据表明口腔上皮细胞通过触发许多诱导坏死性死亡的细胞应激反应来对分泌的真菌毒素念珠菌溶素作出反应。