Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by <named-content content-type="genus-species">Candida albicans</named-content> Hyphae

ABSTRACT Candida albicans is an opportunistic fungal pathogen that can cause life-threatening infections, particularly in immunocompromised patients. C. albicans induced activation of the Nlrp3 inflammasome, leading to secretion of bioactive interleukin 1β (IL-1β) is a crucial myeloid cell immune re...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ona Rogiers, Ulrika C. Frising, Soňa Kucharíková, Mary Ann Jabra-Rizk, Geert van Loo, Patrick Van Dijck, Andy Wullaert
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Candida albicans NLRP3 candidalysin inflammasome primary macrophages Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/91d7d7e56ef642aeae005f9ab147cfa5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:91d7d7e56ef642aeae005f9ab147cfa5
record_format	dspace
spelling	oai:doaj.org-article:91d7d7e56ef642aeae005f9ab147cfa52021-11-15T15:55:14ZCandidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by <named-content content-type="genus-species">Candida albicans</named-content> Hyphae10.1128/mBio.02221-182150-7511https://doaj.org/article/91d7d7e56ef642aeae005f9ab147cfa52019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02221-18https://doaj.org/toc/2150-7511ABSTRACT Candida albicans is an opportunistic fungal pathogen that can cause life-threatening infections, particularly in immunocompromised patients. C. albicans induced activation of the Nlrp3 inflammasome, leading to secretion of bioactive interleukin 1β (IL-1β) is a crucial myeloid cell immune response needed for antifungal host defense. Being a pleiomorphic fungus, C. albicans can provoke Nlrp3 inflammasome responses only upon morphological transformation to its hyphal appearance. However, the specific hyphal factors that enable C. albicans to activate the Nlrp3 inflammasome in primary macrophages remain to be revealed. Here, we identify candidalysin, a peptide derived from the hypha-specific ECE1 gene, as a fungal trigger for Nlrp3 inflammasome-mediated maturation and secretion of IL-1β from primary macrophages. Direct peptide administration experiments showed that candidalysin was sufficient for inducing secretion of mature IL-1β from macrophages in an Nlrp3 inflammasome-dependent manner. Conversely, infection experiments using candidalysin-deficient C. albicans showed that candidalysin crucially contributed to the capacity of this fungus to induce maturation and secretion of IL-1β from primary macrophages. These complementary observations identify the expression of candidalysin as one of the molecular mechanisms by which hyphal transformation equips C. albicans with its proinflammatory capacity to elicit the release of bioactive IL-1β from macrophages. IMPORTANCE Candidiasis is a potentially lethal condition that is caused by systemic dissemination of Candida albicans, a common fungal commensal residing mostly on mucosal surfaces. The transition of C. albicans from an innocuous commensal to an opportunistic pathogen goes hand in hand with its morphological transformation from a fungus to a hyphal appearance. On the one hand, the latter manifestation enables C. albicans to penetrate tissues, while on the other hand, the expression of many hypha-specific genes also endows it with the capacity to trigger particular cytokine responses. The Nlrp3 inflammasome is a crucial component of the innate immune system that provokes release of the IL-1β cytokine from myeloid cells upon encountering C. albicans hyphae. Our study reveals the peptide candidalysin as one of the hypha-derived drivers of Nlrp3 inflammasome responses in primary macrophages and, thus, contributes to better understanding the fungal mechanisms that determine the pathogenicity of C. albicans.Ona RogiersUlrika C. FrisingSoňa KucharíkováMary Ann Jabra-RizkGeert van LooPatrick Van DijckAndy WullaertAmerican Society for MicrobiologyarticleCandida albicansNLRP3candidalysininflammasomeprimary macrophagesMicrobiologyQR1-502ENmBio, Vol 10, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans NLRP3 candidalysin inflammasome primary macrophages Microbiology QR1-502
spellingShingle	Candida albicans NLRP3 candidalysin inflammasome primary macrophages Microbiology QR1-502 Ona Rogiers Ulrika C. Frising Soňa Kucharíková Mary Ann Jabra-Rizk Geert van Loo Patrick Van Dijck Andy Wullaert Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by <named-content content-type="genus-species">Candida albicans</named-content> Hyphae
description	ABSTRACT Candida albicans is an opportunistic fungal pathogen that can cause life-threatening infections, particularly in immunocompromised patients. C. albicans induced activation of the Nlrp3 inflammasome, leading to secretion of bioactive interleukin 1β (IL-1β) is a crucial myeloid cell immune response needed for antifungal host defense. Being a pleiomorphic fungus, C. albicans can provoke Nlrp3 inflammasome responses only upon morphological transformation to its hyphal appearance. However, the specific hyphal factors that enable C. albicans to activate the Nlrp3 inflammasome in primary macrophages remain to be revealed. Here, we identify candidalysin, a peptide derived from the hypha-specific ECE1 gene, as a fungal trigger for Nlrp3 inflammasome-mediated maturation and secretion of IL-1β from primary macrophages. Direct peptide administration experiments showed that candidalysin was sufficient for inducing secretion of mature IL-1β from macrophages in an Nlrp3 inflammasome-dependent manner. Conversely, infection experiments using candidalysin-deficient C. albicans showed that candidalysin crucially contributed to the capacity of this fungus to induce maturation and secretion of IL-1β from primary macrophages. These complementary observations identify the expression of candidalysin as one of the molecular mechanisms by which hyphal transformation equips C. albicans with its proinflammatory capacity to elicit the release of bioactive IL-1β from macrophages. IMPORTANCE Candidiasis is a potentially lethal condition that is caused by systemic dissemination of Candida albicans, a common fungal commensal residing mostly on mucosal surfaces. The transition of C. albicans from an innocuous commensal to an opportunistic pathogen goes hand in hand with its morphological transformation from a fungus to a hyphal appearance. On the one hand, the latter manifestation enables C. albicans to penetrate tissues, while on the other hand, the expression of many hypha-specific genes also endows it with the capacity to trigger particular cytokine responses. The Nlrp3 inflammasome is a crucial component of the innate immune system that provokes release of the IL-1β cytokine from myeloid cells upon encountering C. albicans hyphae. Our study reveals the peptide candidalysin as one of the hypha-derived drivers of Nlrp3 inflammasome responses in primary macrophages and, thus, contributes to better understanding the fungal mechanisms that determine the pathogenicity of C. albicans.
format	article
author	Ona Rogiers Ulrika C. Frising Soňa Kucharíková Mary Ann Jabra-Rizk Geert van Loo Patrick Van Dijck Andy Wullaert
author_facet	Ona Rogiers Ulrika C. Frising Soňa Kucharíková Mary Ann Jabra-Rizk Geert van Loo Patrick Van Dijck Andy Wullaert
author_sort	Ona Rogiers
title	Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by <named-content content-type="genus-species">Candida albicans</named-content> Hyphae
title_short	Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by <named-content content-type="genus-species">Candida albicans</named-content> Hyphae
title_full	Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by <named-content content-type="genus-species">Candida albicans</named-content> Hyphae
title_fullStr	Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by <named-content content-type="genus-species">Candida albicans</named-content> Hyphae
title_full_unstemmed	Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by <named-content content-type="genus-species">Candida albicans</named-content> Hyphae
title_sort	candidalysin crucially contributes to nlrp3 inflammasome activation by <named-content content-type="genus-species">candida albicans</named-content> hyphae
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/91d7d7e56ef642aeae005f9ab147cfa5
work_keys_str_mv	AT onarogiers candidalysincruciallycontributestonlrp3inflammasomeactivationbynamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenthyphae AT ulrikacfrising candidalysincruciallycontributestonlrp3inflammasomeactivationbynamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenthyphae AT sonakucharikova candidalysincruciallycontributestonlrp3inflammasomeactivationbynamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenthyphae AT maryannjabrarizk candidalysincruciallycontributestonlrp3inflammasomeactivationbynamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenthyphae AT geertvanloo candidalysincruciallycontributestonlrp3inflammasomeactivationbynamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenthyphae AT patrickvandijck candidalysincruciallycontributestonlrp3inflammasomeactivationbynamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenthyphae AT andywullaert candidalysincruciallycontributestonlrp3inflammasomeactivationbynamedcontentcontenttypegenusspeciescandidaalbicansnamedcontenthyphae
_version_	1718427230784192512

Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by <named-content content-type="genus-species">Candida albicans</named-content> Hyphae

Ejemplares similares