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Candida albicans induces neutrophil extracellular traps and leucotoxic hypercitrullination via candidalysin
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
School of Cellular and Molecular Medicine, University of Bristol, Bristol, United Kingdom.
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2023 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 24, no 11, article id e57571Article in journal (Refereed) Published
Abstract [en]

The peptide toxin candidalysin, secreted by Candida albicans hyphae, promotes stimulation of neutrophil extracellular traps (NETs). However, candidalysin alone triggers a distinct mechanism for NET-like structures (NLS), which are more compact and less fibrous than canonical NETs. Candidalysin activates NADPH oxidase and calcium influx, with both processes contributing to morphological changes in neutrophils resulting in NLS formation. NLS are induced by leucotoxic hypercitrullination, which is governed by calcium-induced protein arginine deaminase 4 activation and initiation of intracellular signalling events in a dose- and time-dependent manner. However, activation of signalling by candidalysin does not suffice to trigger downstream events essential for NET formation, as demonstrated by lack of lamin A/C phosphorylation, an event required for activation of cyclin-dependent kinases that are crucial for NET release. Candidalysin-triggered NLS demonstrate anti-Candida activity, which is resistant to nuclease treatment and dependent on the deprivation of Zn2+. This study reveals that C. albicans hyphae releasing candidalysin concurrently trigger canonical NETs and NLS, which together form a fibrous sticky network that entangles C. albicans hyphae and efficiently inhibits their growth.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023. Vol. 24, no 11, article id e57571
Keywords [en]
chronic granulomatous disease, fungal immunology, histone citrullination, polymorphonuclear leucocytes, reactive oxygen species
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-215387DOI: 10.15252/embr.202357571ISI: 001081020500001PubMedID: 37795769Scopus ID: 2-s2.0-85173538219OAI: oai:DiVA.org:umu-215387DiVA, id: diva2:1808037
Funder
Swedish Research Council, VR-MH2018-05909Swedish Research Council, VR-MH2020-01764Swedish Research Council, VR-MH2022-00850The Kempe Foundations, CK-2033,U16Wellcome trust, 214229_Z_18_ZGerman Research Foundation (DFG), 390713860Swedish Research Council, 2019-01123Swedish Heart Lung Foundation, 2019-01123Stiftelsen Konung Gustaf V:s 80-årsfondRegion Västra Götaland, TUAGBG-917531Available from: 2023-10-30 Created: 2023-10-30 Last updated: 2024-01-04Bibliographically approved

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Unger, LucasSkoluda, SamuelBackman, EmelieYellagunda, SujanUrban, Constantin F.

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