Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic Cells

The production of IL-1-family cytokines such as IL-1β and IL-18 is finely regulated by inflammasome activation after the recognition of pathogens associated molecular pattern (PAMPs) and danger associated molecular patterns (DAMPs). However, little is known about the helminth-derived molecules capab...

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Autores: Celias, Daiana P., Corvo, Ileana, Silvane, Leonardo, Tort, José F., Chiapello, Laura, S., Fresno, Manuel, Arranz, Alicia, Motrán, Claudia C., Cervi, Laura
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/214045
Acceso en línea:http://hdl.handle.net/10261/214045
Access Level:acceso abierto
Palabra clave:Cathepsin L3
Fasciola hepatica
Dendritic cells
NLRP3 inflammasome
IL-1β
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spelling Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic CellsCelias, Daiana P.Corvo, IleanaSilvane, LeonardoTort, José F.Chiapello, Laura, S.Fresno, ManuelArranz, AliciaMotrán, Claudia C.Cervi, LauraCathepsin L3Fasciola hepaticaDendritic cellsNLRP3 inflammasomeIL-1βThe production of IL-1-family cytokines such as IL-1β and IL-18 is finely regulated by inflammasome activation after the recognition of pathogens associated molecular pattern (PAMPs) and danger associated molecular patterns (DAMPs). However, little is known about the helminth-derived molecules capable of activating the inflammasome. In the case of the helminth trematode Fasciola hepatica, the secretion of different cathepsin L cysteine peptidases (FhCL) is crucial for the parasite survival. Among these enzymes, cathepsin L3 (FhCL3) is expressed mainly in the juvenile or invasive stage. The ability of FhCL3 to digest collagen has demonstrated to be critical for intestinal tissue invasion during juvenile larvae migration. However, there is no information about the interaction of FhCL3 with the immune system. It has been shown here that FhCL3 induces a non-canonical inflammasome activation in dendritic cells (DCs), leading to IL-1β and IL-18 production without a previous microbial priming. Interestingly, this activation was depending on the cysteine protease activity of FhCL3 and the NLRP3 receptor, but independent of caspase activation. We also show that FhCL3 is internalized by DCs, promoting pro-IL-1β cleavage to its mature and biologically active form IL-1β, which is released to the extracellular environment. The FhCL3-induced NLRP3 inflammasome activation conditions DCs to promote a singular adaptive immune response, characterized by increased production of IFN-γ and IL-13. These data reveal an unexpected ability of FhCL3, a helminth-derived molecule, to activate the NLRP3 inflammasome, which is independent of the classical mechanism involving caspase activation.Consejo Nacional de Investigaciones Científicas y Técnicas of Argentina (CONICET) PIP 2015–2017 GI, 112201 501002 60CO, Agencia Nacional de Promoción Científica y Técnica (PICT-2015-1179 and 2488), and Secretaría de Ciencia y Técnica-Universidad Nacional de Córdoba (Argentina)Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina)Agencia Nacional de Promoción Científica y Tecnológica (Argentina)Universidad Nacional de Córdoba (Argentina)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/214045reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3389/fimmu.2019.00552Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2140452026-05-22T06:33:51Z
dc.title.none.fl_str_mv Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic Cells
title Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic Cells
spellingShingle Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic Cells
Celias, Daiana P.
Cathepsin L3
Fasciola hepatica
Dendritic cells
NLRP3 inflammasome
IL-1β
title_short Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic Cells
title_full Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic Cells
title_fullStr Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic Cells
title_full_unstemmed Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic Cells
title_sort Cathepsin L3 From Fasciola hepatica Induces NLRP3 Inflammasome Alternative Activation in Murine Dendritic Cells
dc.creator.none.fl_str_mv Celias, Daiana P.
Corvo, Ileana
Silvane, Leonardo
Tort, José F.
Chiapello, Laura, S.
Fresno, Manuel
Arranz, Alicia
Motrán, Claudia C.
Cervi, Laura
author Celias, Daiana P.
author_facet Celias, Daiana P.
Corvo, Ileana
Silvane, Leonardo
Tort, José F.
Chiapello, Laura, S.
Fresno, Manuel
Arranz, Alicia
Motrán, Claudia C.
Cervi, Laura
author_role author
author2 Corvo, Ileana
Silvane, Leonardo
Tort, José F.
Chiapello, Laura, S.
Fresno, Manuel
Arranz, Alicia
Motrán, Claudia C.
Cervi, Laura
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Nacional de Investigaciones Científicas y Técnicas (Argentina)
Agencia Nacional de Promoción Científica y Tecnológica (Argentina)
Universidad Nacional de Córdoba (Argentina)
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cathepsin L3
Fasciola hepatica
Dendritic cells
NLRP3 inflammasome
IL-1β
topic Cathepsin L3
Fasciola hepatica
Dendritic cells
NLRP3 inflammasome
IL-1β
description The production of IL-1-family cytokines such as IL-1β and IL-18 is finely regulated by inflammasome activation after the recognition of pathogens associated molecular pattern (PAMPs) and danger associated molecular patterns (DAMPs). However, little is known about the helminth-derived molecules capable of activating the inflammasome. In the case of the helminth trematode Fasciola hepatica, the secretion of different cathepsin L cysteine peptidases (FhCL) is crucial for the parasite survival. Among these enzymes, cathepsin L3 (FhCL3) is expressed mainly in the juvenile or invasive stage. The ability of FhCL3 to digest collagen has demonstrated to be critical for intestinal tissue invasion during juvenile larvae migration. However, there is no information about the interaction of FhCL3 with the immune system. It has been shown here that FhCL3 induces a non-canonical inflammasome activation in dendritic cells (DCs), leading to IL-1β and IL-18 production without a previous microbial priming. Interestingly, this activation was depending on the cysteine protease activity of FhCL3 and the NLRP3 receptor, but independent of caspase activation. We also show that FhCL3 is internalized by DCs, promoting pro-IL-1β cleavage to its mature and biologically active form IL-1β, which is released to the extracellular environment. The FhCL3-induced NLRP3 inflammasome activation conditions DCs to promote a singular adaptive immune response, characterized by increased production of IFN-γ and IL-13. These data reveal an unexpected ability of FhCL3, a helminth-derived molecule, to activate the NLRP3 inflammasome, which is independent of the classical mechanism involving caspase activation.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/214045
url http://hdl.handle.net/10261/214045
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3389/fimmu.2019.00552
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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