The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes.
The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes.
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真菌肽毒素念珠菌溶素可激活NLRP3炎性小体，并导致单核吞噬细胞发生细胞溶解。
DOI：
10.1038/s41467-018-06607-1
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发表时间：
2018-10-15
影响因子：
16.6
通讯作者：
Hube B
中科院分区：
文献类型：
--
作者：
Kasper L;König A;Koenig PA;Gresnigt MS;Westman J;Drummond RA;Lionakis MS;Groß O;Ruland J;Naglik JR;Hube B
入侵微生物的清除需要先天免疫系统的吞噬细胞。然而，成功的病原体已经进化出复杂的策略来逃避免疫杀伤。人类机会致病真菌白色念珠菌可被巨噬细胞有效吞噬，但会导致炎性小体活化、宿主细胞溶解，并在菌丝形成后逃逸。以往的研究表明，C.白色念珠菌是由早期炎性小体依赖性细胞死亡（焦亡）、由于葡萄糖耗尽和生长菌丝刺穿膜而引起的晚期损伤引起的。在这里，我们发现，由菌丝相关基因ECE 1编码的溶细胞肽毒素，既是通过钾流出激活NLRP 3炎性小体依赖性caspase-1的中心触发因子，也是感染C.白色念珠菌。这表明，拟南芥素诱导的细胞损伤是C.白色念珠菌介导的单核吞噬细胞死亡，以及由焦亡和消耗葡萄糖的菌丝生长引起的损伤。先天性免疫系统的吞噬细胞在防御包括机会致病菌白色念珠菌在内的入侵病原体中发挥关键作用。在这里，作者表明，C。白色念珠菌衍生的溶藻素除了是单核吞噬细胞的细胞损伤毒素之外，还是这些细胞中NLRP 3炎性体激活的触发物。
Clearance of invading microbes requires phagocytes of the innate immune system. However, successful pathogens have evolved sophisticated strategies to evade immune killing. The opportunistic human fungal pathogen Candida albicans is efficiently phagocytosed by macrophages, but causes inflammasome activation, host cytolysis, and escapes after hypha formation. Previous studies suggest that macrophage lysis by C. albicans results from early inflammasome-dependent cell death (pyroptosis), late damage due to glucose depletion and membrane piercing by growing hyphae. Here we show that Candidalysin, a cytolytic peptide toxin encoded by the hypha-associated gene ECE1, is both a central trigger for NLRP3 inflammasome-dependent caspase-1 activation via potassium efflux and a key driver of inflammasome-independent cytolysis of macrophages and dendritic cells upon infection with C. albicans. This suggests that Candidalysin-induced cell damage is a third mechanism of C. albicans-mediated mononuclear phagocyte cell death in addition to damage caused by pyroptosis and the growth of glucose-consuming hyphae. Phagocytic cells of the innate immune system play critical roles in defence against invading pathogens including the opportunistic pathogen Candida albicans. Here the authors show that C. albicans derived Candidalysin in addition to being a cell-damaging toxin to mononuclear phagocytes is a trigger of NLRP3 inflammasome activation in these cells.
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影响因子：
3.2
作者：
Calvello, Rosa;Mitolo, Vincenzo;Panaro, Maria Antonietta
通讯作者：
Panaro, Maria Antonietta
影响因子：
6.7
作者：
González-Juarbe N;Gilley RP;Hinojosa CA;Bradley KM;Kamei A;Gao G;Dube PH;Bergman MA;Orihuela CJ
通讯作者：
Orihuela CJ
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
3.7
作者：
Autheman D;Wyder M;Popoff M;D'Herde K;Christen S;Posthaus H
通讯作者：
Posthaus H
DOI：
10.1196/annals.1299.107
发表时间：
2003-01-01
期刊：
APOPTOSIS: FROM SIGNALING PATHWAYS TO THERAPEUTIC TOOLS
影响因子：
--
作者：
Ibata-Ombetta, S;Idziorek, T;Jouault, T
通讯作者：
Jouault, T