The escape of Candida albicans from macrophages is enabled by the fungal toxin candidalysin and two host cell death pathways
Details
Publication Year 2022-09-20,Volume 40,Issue #12,Page 111374
Journal Title
Cell Reports
Abstract
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.
Publisher
Cell Press
Keywords
CP: Immunology; CP: Microbiology; Candida albicans; Gasdermin D; Nlrp3; antifungal inflammation; candidalysin; fungal pathogen; hyphae; hyphal escape; inflammasome; macrophage
WEHI Research Division(s)
Inflammation
PubMed ID
36130496
Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2022.111374
Terms of Use/Rights Notice
Refer to copyright notice on published article.


Creation Date: 2022-09-23 10:02:54
Last Modified: 2022-09-23 10:16:02
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