Cathepsin L3 from fasciola hepatica induces NLRP3 inflammasome alternative activation in murine dendritic cells

Autores
Celias, Daiana Pamela; Corvo, Ileana; Silvane, Leonardo Micael; Tort, José Francisco; Chiapello, Laura Silvina; Fresno, Manuel; Arranz, Alicia; Motran, Claudia Cristina; Cervi, Laura Alejandra
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Celias, Daiana Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Corvo, Ileana. Universidad de la República; Uruguay
Fil: Silvane, Leonardo Micael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Tort, José Francisco. Universidad de la República; Uruguay
Fil: Chiapello, Laura Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Fresno, Manuel. Centro de Biología Molecular Severo Ochoa; España
Fil: Arranz, Alicia. Centro de Biología Molecular Severo Ochoa; España
Fil: Motran, Claudia Cristina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Materia
CATHEPSIN L3
DENDRITIC CELLS
FASCIOLA HEPATICA
IL-1Β
NLRP3 INFLAMMASOME
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/128818
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/128818
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cathepsin L3 from fasciola hepatica induces NLRP3 inflammasome alternative activation in murine dendritic cellsCelias, Daiana PamelaCorvo, IleanaSilvane, Leonardo MicaelTort, José FranciscoChiapello, Laura SilvinaFresno, ManuelArranz, AliciaMotran, Claudia CristinaCervi, Laura AlejandraCATHEPSIN L3DENDRITIC CELLSFASCIOLA HEPATICAIL-1ΒNLRP3 INFLAMMASOMEhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3The 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.Fil: Celias, Daiana Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Corvo, Ileana. Universidad de la República; UruguayFil: Silvane, Leonardo Micael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Tort, José Francisco. Universidad de la República; UruguayFil: Chiapello, Laura Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Fresno, Manuel. Centro de Biología Molecular Severo Ochoa; EspañaFil: Arranz, Alicia. Centro de Biología Molecular Severo Ochoa; EspañaFil: Motran, Claudia Cristina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFrontiers Media S.A.2019-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/128818Celias, Daiana Pamela; Corvo, Ileana; Silvane, Leonardo Micael; Tort, José Francisco; Chiapello, Laura Silvina; et al.; Cathepsin L3 from fasciola hepatica induces NLRP3 inflammasome alternative activation in murine dendritic cells; Frontiers Media S.A.; Frontiers in Immunology; 10; MAR; 3-2019; 552-5621664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2019.00552/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.00552info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:53:30Zoai:ri.conicet.gov.ar:11336/128818instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:53:30.951CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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 Pamela
CATHEPSIN L3
DENDRITIC CELLS
FASCIOLA HEPATICA
IL-1Β
NLRP3 INFLAMMASOME
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 Pamela
Corvo, Ileana
Silvane, Leonardo Micael
Tort, José Francisco
Chiapello, Laura Silvina
Fresno, Manuel
Arranz, Alicia
Motran, Claudia Cristina
Cervi, Laura Alejandra
author Celias, Daiana Pamela
author_facet Celias, Daiana Pamela
Corvo, Ileana
Silvane, Leonardo Micael
Tort, José Francisco
Chiapello, Laura Silvina
Fresno, Manuel
Arranz, Alicia
Motran, Claudia Cristina
Cervi, Laura Alejandra
author_role author
author2 Corvo, Ileana
Silvane, Leonardo Micael
Tort, José Francisco
Chiapello, Laura Silvina
Fresno, Manuel
Arranz, Alicia
Motran, Claudia Cristina
Cervi, Laura Alejandra
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv CATHEPSIN L3
DENDRITIC CELLS
FASCIOLA HEPATICA
IL-1Β
NLRP3 INFLAMMASOME
topic CATHEPSIN L3
DENDRITIC CELLS
FASCIOLA HEPATICA
IL-1Β
NLRP3 INFLAMMASOME
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
Fil: Celias, Daiana Pamela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Corvo, Ileana. Universidad de la República; Uruguay
Fil: Silvane, Leonardo Micael. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Tort, José Francisco. Universidad de la República; Uruguay
Fil: Chiapello, Laura Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Fresno, Manuel. Centro de Biología Molecular Severo Ochoa; España
Fil: Arranz, Alicia. Centro de Biología Molecular Severo Ochoa; España
Fil: Motran, Claudia Cristina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Cervi, Laura Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
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 2019-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/128818
Celias, Daiana Pamela; Corvo, Ileana; Silvane, Leonardo Micael; Tort, José Francisco; Chiapello, Laura Silvina; et al.; Cathepsin L3 from fasciola hepatica induces NLRP3 inflammasome alternative activation in murine dendritic cells; Frontiers Media S.A.; Frontiers in Immunology; 10; MAR; 3-2019; 552-562
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/128818
identifier_str_mv Celias, Daiana Pamela; Corvo, Ileana; Silvane, Leonardo Micael; Tort, José Francisco; Chiapello, Laura Silvina; et al.; Cathepsin L3 from fasciola hepatica induces NLRP3 inflammasome alternative activation in murine dendritic cells; Frontiers Media S.A.; Frontiers in Immunology; 10; MAR; 3-2019; 552-562
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/article/10.3389/fimmu.2019.00552/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2019.00552
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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