Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells

Host released alarmins and antimicrobial peptides (AMPs) are highly effective as antifungal agents and inducers. Whilst some are expressed constitutively at mucosal tissues, the primary site of many infections, others are elicited in response to pathogens. In the context of <i>Candida albicans...

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Main Authors: Jemima Ho, Don N. Wickramasinghe, Spyridoula-Angeliki Nikou, Bernhard Hube, Jonathan P. Richardson, Julian R. Naglik
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/9/3/699
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author Jemima Ho
Don N. Wickramasinghe
Spyridoula-Angeliki Nikou
Bernhard Hube
Jonathan P. Richardson
Julian R. Naglik
author_facet Jemima Ho
Don N. Wickramasinghe
Spyridoula-Angeliki Nikou
Bernhard Hube
Jonathan P. Richardson
Julian R. Naglik
author_sort Jemima Ho
collection DOAJ
description Host released alarmins and antimicrobial peptides (AMPs) are highly effective as antifungal agents and inducers. Whilst some are expressed constitutively at mucosal tissues, the primary site of many infections, others are elicited in response to pathogens. In the context of <i>Candida albicans</i>, the fungal factors inducing the release of these innate immune molecules are poorly defined. Herein, we identify candidalysin as a potent trigger of several key alarmins and AMPs known to possess potent anti-<i>Candida</i> functions. We also find extracellular ATP to be an important activator of candidalysin-induced epithelial signalling responses, namely epidermal growth factor receptor (EGFR) and MAPK signalling, which mediate downstream innate immunity during oral epithelial infection. The data provide novel mechanistic insight into the induction of multiple key alarmins and AMPs, important for antifungal defences against <i>C. albicans</i>.
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spelling doaj.art-ec668f7636e94b7ca8c888cc55f436a62023-09-03T05:27:59ZengMDPI AGCells2073-44092020-03-019369910.3390/cells9030699cells9030699Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial CellsJemima Ho0Don N. Wickramasinghe1Spyridoula-Angeliki Nikou2Bernhard Hube3Jonathan P. Richardson4Julian R. Naglik5Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral &amp; Craniofacial Sciences, King’s College London, London SE1 1UL, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral &amp; Craniofacial Sciences, King’s College London, London SE1 1UL, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral &amp; Craniofacial Sciences, King’s College London, London SE1 1UL, UKDepartment of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology–Hans Knöll Institute (HKI), 07745 Jena, GermanyCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral &amp; Craniofacial Sciences, King’s College London, London SE1 1UL, UKCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral &amp; Craniofacial Sciences, King’s College London, London SE1 1UL, UKHost released alarmins and antimicrobial peptides (AMPs) are highly effective as antifungal agents and inducers. Whilst some are expressed constitutively at mucosal tissues, the primary site of many infections, others are elicited in response to pathogens. In the context of <i>Candida albicans</i>, the fungal factors inducing the release of these innate immune molecules are poorly defined. Herein, we identify candidalysin as a potent trigger of several key alarmins and AMPs known to possess potent anti-<i>Candida</i> functions. We also find extracellular ATP to be an important activator of candidalysin-induced epithelial signalling responses, namely epidermal growth factor receptor (EGFR) and MAPK signalling, which mediate downstream innate immunity during oral epithelial infection. The data provide novel mechanistic insight into the induction of multiple key alarmins and AMPs, important for antifungal defences against <i>C. albicans</i>.https://www.mdpi.com/2073-4409/9/3/699<i>candida</i>candidalysinantimicrobial peptidealarminatpdefensin
spellingShingle Jemima Ho
Don N. Wickramasinghe
Spyridoula-Angeliki Nikou
Bernhard Hube
Jonathan P. Richardson
Julian R. Naglik
Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells
Cells
<i>candida</i>
candidalysin
antimicrobial peptide
alarmin
atp
defensin
title Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells
title_full Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells
title_fullStr Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells
title_full_unstemmed Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells
title_short Candidalysin Is a Potent Trigger of Alarmin and Antimicrobial Peptide Release in Epithelial Cells
title_sort candidalysin is a potent trigger of alarmin and antimicrobial peptide release in epithelial cells
topic <i>candida</i>
candidalysin
antimicrobial peptide
alarmin
atp
defensin
url https://www.mdpi.com/2073-4409/9/3/699
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AT spyridoulaangelikinikou candidalysinisapotenttriggerofalarminandantimicrobialpeptidereleaseinepithelialcells
AT bernhardhube candidalysinisapotenttriggerofalarminandantimicrobialpeptidereleaseinepithelialcells
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