上睑下垂
炎症体
巨噬细胞
白色念珠菌
菌丝
细胞生物学
微生物学
细胞外
生物
炎症
程序性细胞死亡
细胞凋亡
免疫学
生物化学
体外
作者
Françios A.B. Olivier,Volker Hilsenstein,Harshini Weerasinghe,Ashley Weir,Sebastian Hughes,Simon Crawford,James E. Vince,Michael J. Hickey,Ana Traven
出处
期刊:Cell Reports
[Elsevier]
日期:2022-09-01
卷期号:40 (12): 111374-111374
被引量:15
标识
DOI:10.1016/j.celrep.2022.111374
摘要
The egress of Candida hyphae from macrophages facilitates immune evasion, but it also alerts macrophages to infection and triggers inflammation. To better define the mechanisms, here we develop an imaging assay to directly and dynamically quantify hyphal escape and correlate it to macrophage responses. The assay reveals that Candida escapes by using two pore-forming proteins to permeabilize macrophage membranes: the fungal toxin candidalysin and Nlrp3 inflammasome-activated Gasdermin D. Candidalysin plays a major role in escape, with Nlrp3 and Gasdermin D-dependent and -independent contributions. The inactivation of Nlrp3 does not reduce hyphal escape, and we identify ETosis via macrophage extracellular trap formation as an additional pathway facilitating hyphal escape. Suppressing hyphal escape does not reduce fungal loads, but it does reduce inflammatory activation. Our findings explain how Candida escapes from macrophages by using three strategies: permeabilizing macrophage membranes via candidalysin and engaging two host cell death pathways, Gasdermin D-mediated pyroptosis and ETosis.
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