NLRP3 Inflammasome Activation by Paracoccidioides brasiliensis

Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis that is geographically confined to Latin America. The pro-inflammatory cytokine IL-1β that is mainly derived from the activation of the cytoplasmic multiprotein complex inflamma...

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Main Authors: Tavares, Aldo Henrique, Magalhães, Kelly Grace, Almeida, Raquel Das Neves, Correa, Rafael, Burgel, Pedro Henrique, Bocca, Anamélia Lorenzetti
Format: Online
Language:English
Published: Public Library of Science 2013
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855149/
id pubmed-3855149
recordtype oai_dc
spelling pubmed-38551492013-12-11 NLRP3 Inflammasome Activation by Paracoccidioides brasiliensis Tavares, Aldo Henrique Magalhães, Kelly Grace Almeida, Raquel Das Neves Correa, Rafael Burgel, Pedro Henrique Bocca, Anamélia Lorenzetti Research Article Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis that is geographically confined to Latin America. The pro-inflammatory cytokine IL-1β that is mainly derived from the activation of the cytoplasmic multiprotein complex inflammasome is an essential host factor against opportunistic fungal infections; however, its role in infection with a primary fungal pathogen, such as P. brasiliensis, is not well understood. In this study, we found that murine bone marrow-derived dendritic cells responded to P. brasiliensis yeast cells infection by releasing IL-1β in a spleen tyrosine kinase (Syk), caspase-1 and NOD-like receptor (NLR) family member NLRP3 dependent manner. In addition, P. brasiliensis-induced NLRP3 inflammasome activation was dependent on potassium (K+) efflux, reactive oxygen species production, phagolysosomal acidification and cathepsin B release. Finally, using mice lacking the IL-1 receptor, we demonstrated that IL-1β signaling has an important role in killing P. brasiliensis by murine macrophages. Altogether, our results demonstrate that the NLRP3 inflammasome senses and responds to P. brasiliensis yeast cells infection and plays an important role in host defense against this fungus. Public Library of Science 2013-12-05 /pmc/articles/PMC3855149/ /pubmed/24340123 http://dx.doi.org/10.1371/journal.pntd.0002595 Text en © 2013 Tavares et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Tavares, Aldo Henrique
Magalhães, Kelly Grace
Almeida, Raquel Das Neves
Correa, Rafael
Burgel, Pedro Henrique
Bocca, Anamélia Lorenzetti
spellingShingle Tavares, Aldo Henrique
Magalhães, Kelly Grace
Almeida, Raquel Das Neves
Correa, Rafael
Burgel, Pedro Henrique
Bocca, Anamélia Lorenzetti
NLRP3 Inflammasome Activation by Paracoccidioides brasiliensis
author_facet Tavares, Aldo Henrique
Magalhães, Kelly Grace
Almeida, Raquel Das Neves
Correa, Rafael
Burgel, Pedro Henrique
Bocca, Anamélia Lorenzetti
author_sort Tavares, Aldo Henrique
title NLRP3 Inflammasome Activation by Paracoccidioides brasiliensis
title_short NLRP3 Inflammasome Activation by Paracoccidioides brasiliensis
title_full NLRP3 Inflammasome Activation by Paracoccidioides brasiliensis
title_fullStr NLRP3 Inflammasome Activation by Paracoccidioides brasiliensis
title_full_unstemmed NLRP3 Inflammasome Activation by Paracoccidioides brasiliensis
title_sort nlrp3 inflammasome activation by paracoccidioides brasiliensis
description Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis (PCM), the most prevalent systemic mycosis that is geographically confined to Latin America. The pro-inflammatory cytokine IL-1β that is mainly derived from the activation of the cytoplasmic multiprotein complex inflammasome is an essential host factor against opportunistic fungal infections; however, its role in infection with a primary fungal pathogen, such as P. brasiliensis, is not well understood. In this study, we found that murine bone marrow-derived dendritic cells responded to P. brasiliensis yeast cells infection by releasing IL-1β in a spleen tyrosine kinase (Syk), caspase-1 and NOD-like receptor (NLR) family member NLRP3 dependent manner. In addition, P. brasiliensis-induced NLRP3 inflammasome activation was dependent on potassium (K+) efflux, reactive oxygen species production, phagolysosomal acidification and cathepsin B release. Finally, using mice lacking the IL-1 receptor, we demonstrated that IL-1β signaling has an important role in killing P. brasiliensis by murine macrophages. Altogether, our results demonstrate that the NLRP3 inflammasome senses and responds to P. brasiliensis yeast cells infection and plays an important role in host defense against this fungus.
publisher Public Library of Science
publishDate 2013
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855149/
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