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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: Ma, Haiyan, Chan, Jasper F. W., Tan, Yen Pei, Kui, Lin, Tsang, Chi-Ching, Pei, Steven L. C., Lau, Yu-Lung, Woo, Patrick C. Y., Lee, Pamela P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666893/
https://www.ncbi.nlm.nih.gov/pubmed/34912336
http://dx.doi.org/10.3389/fimmu.2021.760095
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author Ma, Haiyan
Chan, Jasper F. W.
Tan, Yen Pei
Kui, Lin
Tsang, Chi-Ching
Pei, Steven L. C.
Lau, Yu-Lung
Woo, Patrick C. Y.
Lee, Pamela P.
author_facet Ma, Haiyan
Chan, Jasper F. W.
Tan, Yen Pei
Kui, Lin
Tsang, Chi-Ching
Pei, Steven L. C.
Lau, Yu-Lung
Woo, Patrick C. Y.
Lee, Pamela P.
author_sort Ma, Haiyan
collection PubMed
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.
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spelling pubmed-86668932021-12-14 NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection Ma, Haiyan Chan, Jasper F. W. Tan, Yen Pei Kui, Lin Tsang, Chi-Ching Pei, Steven L. C. Lau, Yu-Lung Woo, Patrick C. Y. Lee, Pamela P. Front Immunol Immunology 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. Frontiers Media S.A. 2021-11-29 /pmc/articles/PMC8666893/ /pubmed/34912336 http://dx.doi.org/10.3389/fimmu.2021.760095 Text en Copyright © 2021 Ma, Chan, Tan, Kui, Tsang, Pei, Lau, Woo and Lee https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ma, Haiyan
Chan, Jasper F. W.
Tan, Yen Pei
Kui, Lin
Tsang, Chi-Ching
Pei, Steven L. C.
Lau, Yu-Lung
Woo, Patrick C. Y.
Lee, Pamela P.
NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection
title 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_short NLRP3 Inflammasome Contributes to Host Defense Against Talaromyces marneffei Infection
title_sort nlrp3 inflammasome contributes to host defense against talaromyces marneffei infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8666893/
https://www.ncbi.nlm.nih.gov/pubmed/34912336
http://dx.doi.org/10.3389/fimmu.2021.760095
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