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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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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. |
format | Online Article Text |
id | pubmed-8666893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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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