Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response

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 proliferat...

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Autores: Nicolao, María Celeste, Rodríguez Rodrígues, Christian Fernando Ariel, Coccimiglio, Magalí Belén, Ledo, Camila, Docena, Guillermo H., Cumino, Andrea Carina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/224542
Acceso en línea:http://hdl.handle.net/11336/224542
Access Level:acceso abierto
Palabra clave:ALBENDAZOLE
DENDRITIC CELLS
ECHINOCOCCUS GRANULOSUS
IMMUNOMODULATION
METFORMIN
PARASITE–HOST INTERACTION
SMALL EXTRACELLULAR VESICLES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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oai_identifier_str oai:ri.conicet.gov.ar:11336/224542
network_acronym_str AR
network_name_str Argentina
repository_id_str
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
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
topic ALBENDAZOLE
DENDRITIC CELLS
ECHINOCOCCUS GRANULOSUS
IMMUNOMODULATION
METFORMIN
PARASITE–HOST INTERACTION
SMALL EXTRACELLULAR VESICLES
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
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
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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
_version_ 1799195161653149696
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 Técnicas2024-05-08T13:45:01Zoai: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:34982024-05-08 13:45:02.138CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
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