NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection

Talaromyce marneffei is an important thermally dimorphic pathogen causing disseminated mycoses in immunocompromised individuals in southeast Asia. Previous studies have suggested that NLRP3 inflammasome plays a critical role in antifungal immunity. However, the mechanism underlying the role of NLRP3...

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Autores principales:	Haiyan Ma, Jasper F. W. Chan, Yen Pei Tan, Lin Kui, Chi-Ching Tsang, Steven L. C. Pei, Yu-Lung Lau, Patrick C. Y. Woo, Pamela P. Lee
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Talaromyce marneffei dectin-1 caspase-1 NLRP3 inflammasome ASC CD4 T cells Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/2f398a3a74204309994748eb5b28ba86
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spelling	oai:doaj.org-article:2f398a3a74204309994748eb5b28ba862021-12-01T13:11:21ZNLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection1664-322410.3389/fimmu.2021.760095https://doaj.org/article/2f398a3a74204309994748eb5b28ba862021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.760095/fullhttps://doaj.org/toc/1664-3224Talaromyce marneffei is an important thermally dimorphic pathogen causing disseminated mycoses in immunocompromised individuals in southeast Asia. Previous studies have suggested that NLRP3 inflammasome plays a critical role in antifungal immunity. However, the mechanism underlying the role of NLRP3 inflammasome activation in host defense against T. marneffei remains unclear. We show that T. marneffei yeasts but not conidia induce potent IL-1β production. The IL-1β response to T. marneffei yeasts is differently regulated in different cell types; T. marneffei yeasts alone are able to induce IL-1β production in human PBMCs and monocytes, whereas LPS priming is essential for IL-1β response to yeasts. We also find that Dectin-1/Syk signaling pathway mediates pro-IL-1β production, and NLRP3-ASC-caspase-1 inflammasome is assembled to trigger the processing of pro-IL-1β into IL-1β. In vivo, mice deficient in NLRP3 or caspase-1 exhibit higher mortality rate and fungal load compared to wild-type mice after systemic T. marneffei infection, which correlates with the diminished recruitment of CD4 T cells into granulomas in knockout mice. Thus, our study first demonstrates that NLRP3 inflammasome contributes to host defense against T. marneffei infection.Haiyan MaJasper F. W. ChanYen Pei TanLin KuiChi-Ching TsangSteven L. C. PeiYu-Lung LauPatrick C. Y. WooPamela P. LeeFrontiers Media S.A.articleTalaromyce marneffeidectin-1caspase-1NLRP3 inflammasomeASCCD4 T cellsImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Talaromyce marneffei dectin-1 caspase-1 NLRP3 inflammasome ASC CD4 T cells Immunologic diseases. Allergy RC581-607
spellingShingle	Talaromyce marneffei dectin-1 caspase-1 NLRP3 inflammasome ASC CD4 T cells Immunologic diseases. Allergy RC581-607 Haiyan Ma Jasper F. W. Chan Yen Pei Tan Lin Kui Chi-Ching Tsang Steven L. C. Pei Yu-Lung Lau Patrick C. Y. Woo Pamela P. Lee NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection
description	Talaromyce marneffei is an important thermally dimorphic pathogen causing disseminated mycoses in immunocompromised individuals in southeast Asia. Previous studies have suggested that NLRP3 inflammasome plays a critical role in antifungal immunity. However, the mechanism underlying the role of NLRP3 inflammasome activation in host defense against T. marneffei remains unclear. We show that T. marneffei yeasts but not conidia induce potent IL-1β production. The IL-1β response to T. marneffei yeasts is differently regulated in different cell types; T. marneffei yeasts alone are able to induce IL-1β production in human PBMCs and monocytes, whereas LPS priming is essential for IL-1β response to yeasts. We also find that Dectin-1/Syk signaling pathway mediates pro-IL-1β production, and NLRP3-ASC-caspase-1 inflammasome is assembled to trigger the processing of pro-IL-1β into IL-1β. In vivo, mice deficient in NLRP3 or caspase-1 exhibit higher mortality rate and fungal load compared to wild-type mice after systemic T. marneffei infection, which correlates with the diminished recruitment of CD4 T cells into granulomas in knockout mice. Thus, our study first demonstrates that NLRP3 inflammasome contributes to host defense against T. marneffei infection.
format	article
author	Haiyan Ma Jasper F. W. Chan Yen Pei Tan Lin Kui Chi-Ching Tsang Steven L. C. Pei Yu-Lung Lau Patrick C. Y. Woo Pamela P. Lee
author_facet	Haiyan Ma Jasper F. W. Chan Yen Pei Tan Lin Kui Chi-Ching Tsang Steven L. C. Pei Yu-Lung Lau Patrick C. Y. Woo Pamela P. Lee
author_sort	Haiyan Ma
title	NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection
title_short	NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection
title_full	NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection
title_fullStr	NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection
title_full_unstemmed	NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection
title_sort	nlrp3 inflammasome contributes to host defense against talaromyces marneffei infection
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2f398a3a74204309994748eb5b28ba86
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NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection

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