Title |
Candida albicans induces neutrophil extracellular traps and leucotoxic hypercitrullination via candidalysin
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Published in |
EMBO Reports, October 2023
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DOI | 10.15252/embr.202357571 |
Pubmed ID | |
Authors |
Lucas Unger, Samuel Skoluda, Emelie Backman, Borko Amulic, Fernando M Ponce‐Garcia, Chinelo NC Etiaba, Sujan Yellagunda, Renate Krüger, Horst von Bernuth, Johan Bylund, Bernhard Hube, Julian R Naglik, Constantin F Urban |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Germany | 3 | 30% |
United Kingdom | 2 | 20% |
United States | 1 | 10% |
Unknown | 4 | 40% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 6 | 60% |
Scientists | 4 | 40% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 11 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Professor | 2 | 18% |
Professor > Associate Professor | 1 | 9% |
Student > Ph. D. Student | 1 | 9% |
Student > Bachelor | 1 | 9% |
Other | 1 | 9% |
Other | 0 | 0% |
Unknown | 5 | 45% |
Readers by discipline | Count | As % |
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Agricultural and Biological Sciences | 2 | 18% |
Biochemistry, Genetics and Molecular Biology | 1 | 9% |
Unspecified | 1 | 9% |
Immunology and Microbiology | 1 | 9% |
Medicine and Dentistry | 1 | 9% |
Other | 0 | 0% |
Unknown | 5 | 45% |