念珠菌素触发上皮细胞应激诱导坏死死亡

IF 2.6 2区 生物学 Q3 CELL BIOLOGY
Mariana Blagojevic, Giorgio Camilli, Michelle Maxson, Bernhard Hube, David L. Moyes, Jonathan P. Richardson, Julian R. Naglik
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引用次数: 21

摘要

白色念珠菌是一种常见的机会性真菌病原体,可引起从浅表粘膜到血源性弥散性念珠菌病的广泛感染。菌丝形态通过侵入上皮细胞引起组织损伤,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,念珠菌素诱导细胞死亡的机制尚不清楚。在这里,我们检测了念珠菌素对口腔上皮细胞死亡的诱导作用。使用健康/凋亡/坏死细胞标记的荧光成像显示,念珠菌素以浓度依赖的方式引起坏死细胞而不是凋亡细胞数量的快速和显著增加。由于白色念珠菌和念珠菌素未能激活caspase-8和-3,或聚(adp核糖)聚合酶的裂解,因此证实了坏死样途径的激活。此外,念珠菌素处理的口腔上皮细胞表现出活性氧的快速产生,线粒体活性和线粒体膜电位的破坏,ATP的消耗和细胞色素c的释放。总的来说,这些数据表明,口腔上皮细胞对分泌的真菌毒素念珠菌素作出反应,触发许多细胞应激反应,诱导坏死死亡。从白色念珠菌分泌的念珠菌素引起上皮细胞应激。念珠菌素诱导宿主细胞钙内流和氧化应激。念珠菌素诱导线粒体功能障碍、ATP耗竭和上皮坏死。念珠菌素的毒性是通过上皮细胞表面介导的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Candidalysin triggers epithelial cellular stresses that induce necrotic death

Candidalysin triggers epithelial cellular stresses that induce necrotic death

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.

Take aways

  • Candidalysin secreted from Candida albicans causes epithelial cell stress.
  • Candidalysin induces calcium influx and oxidative stress in host cells.
  • Candidalysin induces mitochondrial dysfunction, ATP depletion and epithelial necrosis.
  • The toxicity of candidalysin is mediated from the epithelial cell surface.
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来源期刊
Cellular Microbiology
Cellular Microbiology 生物-微生物学
CiteScore
9.70
自引率
0.00%
发文量
26
审稿时长
3 months
期刊介绍: Cellular Microbiology aims to publish outstanding contributions to the understanding of interactions between microbes, prokaryotes and eukaryotes, and their host in the context of pathogenic or mutualistic relationships, including co-infections and microbiota. We welcome studies on single cells, animals and plants, and encourage the use of model hosts and organoid cultures. Submission on cell and molecular biological aspects of microbes, such as their intracellular organization or the establishment and maintenance of their architecture in relation to virulence and pathogenicity are also encouraged. Contributions must provide mechanistic insights supported by quantitative data obtained through imaging, cellular, biochemical, structural or genetic approaches.
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