Candidalysin triggers epithelial cellular stresses that induce necrotic death.
Candidalysin triggers epithelial cellular stresses that induce necrotic death.
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DOI：
10.1111/cmi.13371
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发表时间：
2021-10
影响因子：
3.4
通讯作者：
Naglik JR
中科院分区：
文献类型：
--
作者：
Blagojevic M;Camilli G;Maxson M;Hube B;Moyes DL;Richardson JP;Naglik JR
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。
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 heathy/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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影响因子：
6.4
作者：
O'Meara TR;Duah K;Guo CX;Maxson ME;Gaudet RG;Koselny K;Wellington M;Powers ME;MacAlpine J;O'Meara MJ;Veri AO;Grinstein S;Noble SM;Krysan D;Gray-Owen SD;Cowen LE
通讯作者：
Cowen LE
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作者：
Cerella C;Diederich M;Ghibelli L
通讯作者：
Ghibelli L
影响因子：
4.8
作者：
Ibata-Ombetta, S;Idziorek, T;Jouault, T
通讯作者：
Jouault, T
影响因子：
16.6
作者：
Kasper L;König A;Koenig PA;Gresnigt MS;Westman J;Drummond RA;Lionakis MS;Groß O;Ruland J;Naglik JR;Hube B
通讯作者：
Hube B
影响因子：
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作者：
Han B;Yao W;Oh YT;Tong JS;Li S;Deng J;Yue P;Khuri FR;Sun SY
通讯作者：
Sun SY