The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome
Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), one of the most prevalent subcutaneous mycosis in tropical and subtropical countries. CBM is a poorly characterized chronic infection that commonly starts after transcutaneous inoculation of conidia and saprophytic hyphae o...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01572/full |
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| author | Raffael Júnio Araújo de Castro Isaque Medeiros Siqueira Márcio Sousa Jerônimo Angelina Maria Moreschi Basso Paulo Henrique de Holanda Veloso Junior Kelly Grace Magalhães Luiza Chaves Leonhardt Stephan Alberto Machado de Oliveira Pedro Henrique Bürgel Aldo Henrique Tavares Anamélia Lorenzetti Bocca |
| author_facet | Raffael Júnio Araújo de Castro Isaque Medeiros Siqueira Márcio Sousa Jerônimo Angelina Maria Moreschi Basso Paulo Henrique de Holanda Veloso Junior Kelly Grace Magalhães Luiza Chaves Leonhardt Stephan Alberto Machado de Oliveira Pedro Henrique Bürgel Aldo Henrique Tavares Anamélia Lorenzetti Bocca |
| author_sort | Raffael Júnio Araújo de Castro |
| collection | DOAJ |
| description | Fonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), one of the most prevalent subcutaneous mycosis in tropical and subtropical countries. CBM is a poorly characterized chronic infection that commonly starts after transcutaneous inoculation of conidia and saprophytic hyphae of F. pedrosoi. Recently, we have shown that unlike conidia, hyphae and muriform cells (the parasitic morphotype) of F. pedrosoi promotes an intense inflammatory response pattern in vivo, which comprises the production of an inflammasome-derived cytokine, IL-1β. Nonetheless, the mechanisms underlying IL-1β production and maturation upon F. pedrosoi infection and its functional output in the course of CBM remains unknown. We show here that F. pedrosoi hyphae, differently from conidia, induce IL-1β secretion in both bone marrow-derived dendritic cells and macrophages. Using inhibitors and knockout cells, we demonstrated that the mechanisms underlying IL-1β production by hyphae-infected macrophages were dependent on dectin-1, -2, and -3 receptors and the Syk-NF-kB signaling pathway. Furthermore, F. pedrosoi promoted a NLRP3-dependent inflammasome activation, which required potassium efflux, reactive oxygen species production, phagolysosomal acidification, and cathepsin B release as triggers. IL-1β processing and release was mediated primarily by caspase-1 and, to a lesser extent, by caspase-8-dependent cleavage. Finally, we showed using a murine CBM model that F. pedrosoi elicits a NLRP3-regulated IL-1β and interleukin-18 release in vivo, but without NLRP3 inflammasome activation interfering in the course of the experimental infection. |
| first_indexed | 2024-12-11T07:44:07Z |
| format | Article |
| id | doaj.art-9b113ed1e4574eb18fd6510cd60abaed |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T07:44:07Z |
| publishDate | 2017-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9b113ed1e4574eb18fd6510cd60abaed2022-12-22T01:15:30ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-11-01810.3389/fimmu.2017.01572306692The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 InflammasomeRaffael Júnio Araújo de Castro0Isaque Medeiros Siqueira1Márcio Sousa Jerônimo2Angelina Maria Moreschi Basso3Paulo Henrique de Holanda Veloso Junior4Kelly Grace Magalhães5Luiza Chaves Leonhardt6Stephan Alberto Machado de Oliveira7Pedro Henrique Bürgel8Aldo Henrique Tavares9Anamélia Lorenzetti Bocca10Laboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Immunology and Inflammation, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilLaboratory of Applied Immunology, Department of Cellular Biology, Institute of Biological Sciences, University of Brasília, Brasília, BrazilFonsecaea pedrosoi is the main etiologic agent of chromoblastomycosis (CBM), one of the most prevalent subcutaneous mycosis in tropical and subtropical countries. CBM is a poorly characterized chronic infection that commonly starts after transcutaneous inoculation of conidia and saprophytic hyphae of F. pedrosoi. Recently, we have shown that unlike conidia, hyphae and muriform cells (the parasitic morphotype) of F. pedrosoi promotes an intense inflammatory response pattern in vivo, which comprises the production of an inflammasome-derived cytokine, IL-1β. Nonetheless, the mechanisms underlying IL-1β production and maturation upon F. pedrosoi infection and its functional output in the course of CBM remains unknown. We show here that F. pedrosoi hyphae, differently from conidia, induce IL-1β secretion in both bone marrow-derived dendritic cells and macrophages. Using inhibitors and knockout cells, we demonstrated that the mechanisms underlying IL-1β production by hyphae-infected macrophages were dependent on dectin-1, -2, and -3 receptors and the Syk-NF-kB signaling pathway. Furthermore, F. pedrosoi promoted a NLRP3-dependent inflammasome activation, which required potassium efflux, reactive oxygen species production, phagolysosomal acidification, and cathepsin B release as triggers. IL-1β processing and release was mediated primarily by caspase-1 and, to a lesser extent, by caspase-8-dependent cleavage. Finally, we showed using a murine CBM model that F. pedrosoi elicits a NLRP3-regulated IL-1β and interleukin-18 release in vivo, but without NLRP3 inflammasome activation interfering in the course of the experimental infection.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01572/fullNLRP3 inflammasomeFonsecaea pedrosoichromoblastomycosishyphaemacrophagesdendritic cells |
| spellingShingle | Raffael Júnio Araújo de Castro Isaque Medeiros Siqueira Márcio Sousa Jerônimo Angelina Maria Moreschi Basso Paulo Henrique de Holanda Veloso Junior Kelly Grace Magalhães Luiza Chaves Leonhardt Stephan Alberto Machado de Oliveira Pedro Henrique Bürgel Aldo Henrique Tavares Anamélia Lorenzetti Bocca The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome Frontiers in Immunology NLRP3 inflammasome Fonsecaea pedrosoi chromoblastomycosis hyphae macrophages dendritic cells |
| title | The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome |
| title_full | The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome |
| title_fullStr | The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome |
| title_full_unstemmed | The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome |
| title_short | The Major Chromoblastomycosis Etiologic Agent Fonsecaea pedrosoi Activates the NLRP3 Inflammasome |
| title_sort | major chromoblastomycosis etiologic agent fonsecaea pedrosoi activates the nlrp3 inflammasome |
| topic | NLRP3 inflammasome Fonsecaea pedrosoi chromoblastomycosis hyphae macrophages dendritic cells |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01572/full |
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