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Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection

BACKGROUND: Candidalysin is a cytolytic peptide toxin secreted by Candida albicans hyphae and has significantly advanced our understanding of fungal pathogenesis. Candidalysin is critical for mucosal C albicans infections and is known to activate epithelial cells to induce downstream innate immune r...

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Autores principales: Swidergall, Marc, Khalaji, Mina, Solis, Norma V, Moyes, David L, Drummond, Rebecca A, Hube, Bernhard, Lionakis, Michail S, Murdoch, Craig, Filler, Scott G, Naglik, Julian R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761979/
https://www.ncbi.nlm.nih.gov/pubmed/31401652
http://dx.doi.org/10.1093/infdis/jiz322
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author Swidergall, Marc
Khalaji, Mina
Solis, Norma V
Moyes, David L
Drummond, Rebecca A
Hube, Bernhard
Lionakis, Michail S
Murdoch, Craig
Filler, Scott G
Naglik, Julian R
author_facet Swidergall, Marc
Khalaji, Mina
Solis, Norma V
Moyes, David L
Drummond, Rebecca A
Hube, Bernhard
Lionakis, Michail S
Murdoch, Craig
Filler, Scott G
Naglik, Julian R
author_sort Swidergall, Marc
collection PubMed
description BACKGROUND: Candidalysin is a cytolytic peptide toxin secreted by Candida albicans hyphae and has significantly advanced our understanding of fungal pathogenesis. Candidalysin is critical for mucosal C albicans infections and is known to activate epithelial cells to induce downstream innate immune responses that are associated with protection or immunopathology during oral or vaginal infections. Furthermore, candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. However, the role of candidalysin in driving systemic infections is unknown. METHODS: In this study, using candidalysin-producing and candidalysin-deficient C albicans strains, we show that candidalysin activates mitogen-activated protein kinase (MAPK) signaling and chemokine secretion in endothelial cells in vitro. RESULTS: Candidalysin induces immune activation and neutrophil recruitment in vivo, and it promotes mortality in zebrafish and murine models of systemic fungal infection. CONCLUSIONS: The data demonstrate a key role for candidalysin in neutrophil recruitment and fungal virulence during disseminated systemic C albicans infections.
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spelling pubmed-67619792019-09-27 Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection Swidergall, Marc Khalaji, Mina Solis, Norma V Moyes, David L Drummond, Rebecca A Hube, Bernhard Lionakis, Michail S Murdoch, Craig Filler, Scott G Naglik, Julian R J Infect Dis Major Articles and Brief Reports BACKGROUND: Candidalysin is a cytolytic peptide toxin secreted by Candida albicans hyphae and has significantly advanced our understanding of fungal pathogenesis. Candidalysin is critical for mucosal C albicans infections and is known to activate epithelial cells to induce downstream innate immune responses that are associated with protection or immunopathology during oral or vaginal infections. Furthermore, candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes. However, the role of candidalysin in driving systemic infections is unknown. METHODS: In this study, using candidalysin-producing and candidalysin-deficient C albicans strains, we show that candidalysin activates mitogen-activated protein kinase (MAPK) signaling and chemokine secretion in endothelial cells in vitro. RESULTS: Candidalysin induces immune activation and neutrophil recruitment in vivo, and it promotes mortality in zebrafish and murine models of systemic fungal infection. CONCLUSIONS: The data demonstrate a key role for candidalysin in neutrophil recruitment and fungal virulence during disseminated systemic C albicans infections. Oxford University Press 2019-11-01 2019-08-11 /pmc/articles/PMC6761979/ /pubmed/31401652 http://dx.doi.org/10.1093/infdis/jiz322 Text en © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Major Articles and Brief Reports
Swidergall, Marc
Khalaji, Mina
Solis, Norma V
Moyes, David L
Drummond, Rebecca A
Hube, Bernhard
Lionakis, Michail S
Murdoch, Craig
Filler, Scott G
Naglik, Julian R
Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection
title Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection
title_full Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection
title_fullStr Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection
title_full_unstemmed Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection
title_short Candidalysin Is Required for Neutrophil Recruitment and Virulence During Systemic Candida albicans Infection
title_sort candidalysin is required for neutrophil recruitment and virulence during systemic candida albicans infection
topic Major Articles and Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761979/
https://www.ncbi.nlm.nih.gov/pubmed/31401652
http://dx.doi.org/10.1093/infdis/jiz322
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