Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response
- Autores
- Nicolao, María Celeste; Rodríguez Rodrígues, Christian Fernando Ariel; Coccimiglio, Magalí Belén; Ledo, Camila; Docena, Guillermo H.; Cumino, Andrea Carina
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background: The Echinococcus granulosus sensu lato species complex causes cystic echinococcosis, a zoonotic disease of medical importance. Parasite-derived small extracellular vesicles (sEVs) are involved in the interaction with hosts intervening in signal transduction related to parasite proliferation and disease pathogenesis. Although the characteristics of sEVs from E. granulosus protoscoleces and their interaction with host dendritic cells (DCs) have been described, the effect of sEVs recovered during parasite pharmacological treatment on the immune response remains unexplored. Methods: Here, we isolated and characterized sEVs from control and drug-treated protoscoleces by ultracentrifugation, transmission electron microscopy, dynamic light scattering, and proteomic analysis. In addition, we evaluated the cytokine response profile induced in murine bone marrow-derived dendritic cells (BMDCs) by qPCR. Results: The isolated sEVs, with conventional size between 50 and 200 nm, regardless of drug treatment, showed more than 500 cargo proteins and, importantly, 20 known antigens and 70 potential antigenic proteins, and several integral-transmembrane and soluble proteins mainly associated with signal transduction, immunomodulation, scaffolding factors, extracellular matrix-anchoring, and lipid transport. The identity and abundance of proteins in the sEV-cargo from metformin- and albendazole sulfoxide (ABZSO)-treated parasites were determined by proteomic analysis, detecting 107 and eight exclusive proteins, respectively, which include proteins related to the mechanisms of drug action. We also determined that the interaction of murine BMDCs with sEVs derived from control parasites and those treated with ABZSO and metformin increased the expression of pro-inflammatory cytokines such as IL-12 compared to control cells. Additionally, protoscolex-derived vesicles from metformin treatments induced the production of IL-6, TNF-α, and IL-10. However, the expression of IL-23 and TGF-β was downregulated. Conclusions: We demonstrated that sEV-cargo derived from drug-treated E. granulosus protoscoleces have immunomodulatory functions, as they enhance DC activation towards a type 1 pro-inflammatory profile against the parasite, and therefore support the proposal of a new approach for the prevention and treatment of secondary echinococcosis.
Fil: Nicolao, María Celeste. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; Argentina
Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina
Fil: Coccimiglio, Magalí Belén. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; Argentina
Fil: Ledo, Camila. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; Argentina
Fil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; Argentina - Materia
-
ALBENDAZOLE
DENDRITIC CELLS
ECHINOCOCCUS GRANULOSUS
IMMUNOMODULATION
METFORMIN
PARASITE–HOST INTERACTION
SMALL EXTRACELLULAR VESICLES - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/224542
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/224542 |
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CONICETDig |
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spelling |
Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune responseNicolao, María CelesteRodríguez Rodrígues, Christian Fernando ArielCoccimiglio, Magalí BelénLedo, CamilaDocena, Guillermo H.Cumino, Andrea CarinaALBENDAZOLEDENDRITIC CELLSECHINOCOCCUS GRANULOSUSIMMUNOMODULATIONMETFORMINPARASITE–HOST INTERACTIONSMALL EXTRACELLULAR VESICLEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: The Echinococcus granulosus sensu lato species complex causes cystic echinococcosis, a zoonotic disease of medical importance. Parasite-derived small extracellular vesicles (sEVs) are involved in the interaction with hosts intervening in signal transduction related to parasite proliferation and disease pathogenesis. Although the characteristics of sEVs from E. granulosus protoscoleces and their interaction with host dendritic cells (DCs) have been described, the effect of sEVs recovered during parasite pharmacological treatment on the immune response remains unexplored. Methods: Here, we isolated and characterized sEVs from control and drug-treated protoscoleces by ultracentrifugation, transmission electron microscopy, dynamic light scattering, and proteomic analysis. In addition, we evaluated the cytokine response profile induced in murine bone marrow-derived dendritic cells (BMDCs) by qPCR. Results: The isolated sEVs, with conventional size between 50 and 200 nm, regardless of drug treatment, showed more than 500 cargo proteins and, importantly, 20 known antigens and 70 potential antigenic proteins, and several integral-transmembrane and soluble proteins mainly associated with signal transduction, immunomodulation, scaffolding factors, extracellular matrix-anchoring, and lipid transport. The identity and abundance of proteins in the sEV-cargo from metformin- and albendazole sulfoxide (ABZSO)-treated parasites were determined by proteomic analysis, detecting 107 and eight exclusive proteins, respectively, which include proteins related to the mechanisms of drug action. We also determined that the interaction of murine BMDCs with sEVs derived from control parasites and those treated with ABZSO and metformin increased the expression of pro-inflammatory cytokines such as IL-12 compared to control cells. Additionally, protoscolex-derived vesicles from metformin treatments induced the production of IL-6, TNF-α, and IL-10. However, the expression of IL-23 and TGF-β was downregulated. Conclusions: We demonstrated that sEV-cargo derived from drug-treated E. granulosus protoscoleces have immunomodulatory functions, as they enhance DC activation towards a type 1 pro-inflammatory profile against the parasite, and therefore support the proposal of a new approach for the prevention and treatment of secondary echinococcosis.Fil: Nicolao, María Celeste. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; ArgentinaFil: Coccimiglio, Magalí Belén. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Ledo, Camila. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaFil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; ArgentinaBioMed Central2023-07-29info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/224542Nicolao, María Celeste; Rodríguez Rodrígues, Christian Fernando Ariel; Coccimiglio, Magalí Belén; Ledo, Camila; Docena, Guillermo H.; et al.; Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response; BioMed Central; Parasites and Vectors; 16; 1; 29-7-2023; 1-151756-3305CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/s13071-023-05854-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:48:26Zoai:ri.conicet.gov.ar:11336/224542instacron: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:34982025-09-29 09:48:27.083CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response |
title |
Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response |
spellingShingle |
Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response Nicolao, María Celeste ALBENDAZOLE DENDRITIC CELLS ECHINOCOCCUS GRANULOSUS IMMUNOMODULATION METFORMIN PARASITE–HOST INTERACTION SMALL EXTRACELLULAR VESICLES |
title_short |
Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response |
title_full |
Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response |
title_fullStr |
Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response |
title_full_unstemmed |
Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response |
title_sort |
Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response |
dc.creator.none.fl_str_mv |
Nicolao, María Celeste Rodríguez Rodrígues, Christian Fernando Ariel Coccimiglio, Magalí Belén Ledo, Camila Docena, Guillermo H. Cumino, Andrea Carina |
author |
Nicolao, María Celeste |
author_facet |
Nicolao, María Celeste Rodríguez Rodrígues, Christian Fernando Ariel Coccimiglio, Magalí Belén Ledo, Camila Docena, Guillermo H. Cumino, Andrea Carina |
author_role |
author |
author2 |
Rodríguez Rodrígues, Christian Fernando Ariel Coccimiglio, Magalí Belén Ledo, Camila Docena, Guillermo H. Cumino, Andrea Carina |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
ALBENDAZOLE DENDRITIC CELLS ECHINOCOCCUS GRANULOSUS IMMUNOMODULATION METFORMIN PARASITE–HOST INTERACTION SMALL EXTRACELLULAR VESICLES |
topic |
ALBENDAZOLE DENDRITIC CELLS ECHINOCOCCUS GRANULOSUS IMMUNOMODULATION METFORMIN PARASITE–HOST INTERACTION SMALL EXTRACELLULAR VESICLES |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Background: The Echinococcus granulosus sensu lato species complex causes cystic echinococcosis, a zoonotic disease of medical importance. Parasite-derived small extracellular vesicles (sEVs) are involved in the interaction with hosts intervening in signal transduction related to parasite proliferation and disease pathogenesis. Although the characteristics of sEVs from E. granulosus protoscoleces and their interaction with host dendritic cells (DCs) have been described, the effect of sEVs recovered during parasite pharmacological treatment on the immune response remains unexplored. Methods: Here, we isolated and characterized sEVs from control and drug-treated protoscoleces by ultracentrifugation, transmission electron microscopy, dynamic light scattering, and proteomic analysis. In addition, we evaluated the cytokine response profile induced in murine bone marrow-derived dendritic cells (BMDCs) by qPCR. Results: The isolated sEVs, with conventional size between 50 and 200 nm, regardless of drug treatment, showed more than 500 cargo proteins and, importantly, 20 known antigens and 70 potential antigenic proteins, and several integral-transmembrane and soluble proteins mainly associated with signal transduction, immunomodulation, scaffolding factors, extracellular matrix-anchoring, and lipid transport. The identity and abundance of proteins in the sEV-cargo from metformin- and albendazole sulfoxide (ABZSO)-treated parasites were determined by proteomic analysis, detecting 107 and eight exclusive proteins, respectively, which include proteins related to the mechanisms of drug action. We also determined that the interaction of murine BMDCs with sEVs derived from control parasites and those treated with ABZSO and metformin increased the expression of pro-inflammatory cytokines such as IL-12 compared to control cells. Additionally, protoscolex-derived vesicles from metformin treatments induced the production of IL-6, TNF-α, and IL-10. However, the expression of IL-23 and TGF-β was downregulated. Conclusions: We demonstrated that sEV-cargo derived from drug-treated E. granulosus protoscoleces have immunomodulatory functions, as they enhance DC activation towards a type 1 pro-inflammatory profile against the parasite, and therefore support the proposal of a new approach for the prevention and treatment of secondary echinococcosis. Fil: Nicolao, María Celeste. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; Argentina Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata; Argentina Fil: Coccimiglio, Magalí Belén. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; Argentina Fil: Ledo, Camila. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; Argentina Fil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentina Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones en Producción, Sanidad y Ambiente; Argentina |
description |
Background: The Echinococcus granulosus sensu lato species complex causes cystic echinococcosis, a zoonotic disease of medical importance. Parasite-derived small extracellular vesicles (sEVs) are involved in the interaction with hosts intervening in signal transduction related to parasite proliferation and disease pathogenesis. Although the characteristics of sEVs from E. granulosus protoscoleces and their interaction with host dendritic cells (DCs) have been described, the effect of sEVs recovered during parasite pharmacological treatment on the immune response remains unexplored. Methods: Here, we isolated and characterized sEVs from control and drug-treated protoscoleces by ultracentrifugation, transmission electron microscopy, dynamic light scattering, and proteomic analysis. In addition, we evaluated the cytokine response profile induced in murine bone marrow-derived dendritic cells (BMDCs) by qPCR. Results: The isolated sEVs, with conventional size between 50 and 200 nm, regardless of drug treatment, showed more than 500 cargo proteins and, importantly, 20 known antigens and 70 potential antigenic proteins, and several integral-transmembrane and soluble proteins mainly associated with signal transduction, immunomodulation, scaffolding factors, extracellular matrix-anchoring, and lipid transport. The identity and abundance of proteins in the sEV-cargo from metformin- and albendazole sulfoxide (ABZSO)-treated parasites were determined by proteomic analysis, detecting 107 and eight exclusive proteins, respectively, which include proteins related to the mechanisms of drug action. We also determined that the interaction of murine BMDCs with sEVs derived from control parasites and those treated with ABZSO and metformin increased the expression of pro-inflammatory cytokines such as IL-12 compared to control cells. Additionally, protoscolex-derived vesicles from metformin treatments induced the production of IL-6, TNF-α, and IL-10. However, the expression of IL-23 and TGF-β was downregulated. Conclusions: We demonstrated that sEV-cargo derived from drug-treated E. granulosus protoscoleces have immunomodulatory functions, as they enhance DC activation towards a type 1 pro-inflammatory profile against the parasite, and therefore support the proposal of a new approach for the prevention and treatment of secondary echinococcosis. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-07-29 |
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/11336/224542 Nicolao, María Celeste; Rodríguez Rodrígues, Christian Fernando Ariel; Coccimiglio, Magalí Belén; Ledo, Camila; Docena, Guillermo H.; et al.; Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response; BioMed Central; Parasites and Vectors; 16; 1; 29-7-2023; 1-15 1756-3305 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/224542 |
identifier_str_mv |
Nicolao, María Celeste; Rodríguez Rodrígues, Christian Fernando Ariel; Coccimiglio, Magalí Belén; Ledo, Camila; Docena, Guillermo H.; et al.; Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response; BioMed Central; Parasites and Vectors; 16; 1; 29-7-2023; 1-15 1756-3305 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1186/s13071-023-05854-6 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
BioMed Central |
publisher.none.fl_str_mv |
BioMed Central |
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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1844613505098973184 |
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13.070432 |