Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition

Autores
Rodríguez Rodrígues, Christian Fernando Ariel; Nicolao, María Celeste; Chop, Maia; Plá, Natalia; Massaro, Mora; Loos, Julia Alexandra; Cumino, Andrea Carina
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Immune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host?s response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.
Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nicolao, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina
Fil: Chop, Maia. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Plá, Natalia. Universidad Nacional de Mar del Plata; Argentina
Fil: Massaro, Mora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina
Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cumino, Andrea Carina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina
Materia
ECHINOCOCCUS GRANULOSUS
DENDRITIC CELL
T-CELL
INMUNOMODULATION
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:11336/230088
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/230088
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognitionRodríguez Rodrígues, Christian Fernando ArielNicolao, María CelesteChop, MaiaPlá, NataliaMassaro, MoraLoos, Julia AlexandraCumino, Andrea CarinaECHINOCOCCUS GRANULOSUSDENDRITIC CELLT-CELLINMUNOMODULATIONhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Immune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host?s response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Nicolao, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Chop, Maia. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Plá, Natalia. Universidad Nacional de Mar del Plata; ArgentinaFil: Massaro, Mora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; ArgentinaFil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cumino, Andrea Carina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; ArgentinaNature Research2020-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/230088Rodríguez Rodrígues, Christian Fernando Ariel; Nicolao, María Celeste; Chop, Maia; Plá, Natalia; Massaro, Mora; et al.; Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition; Nature Research; Scientific Reports; 11; 1; 7-2020; 1-152045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.biorxiv.org/content/10.1101/2020.07.27.224055v1.abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-021-96435-zinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:07:37Zoai:ri.conicet.gov.ar:11336/230088instacron: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 10:07:38.175CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
spellingShingle Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
Rodríguez Rodrígues, Christian Fernando Ariel
ECHINOCOCCUS GRANULOSUS
DENDRITIC CELL
T-CELL
INMUNOMODULATION
title_short Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title_full Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title_fullStr Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title_full_unstemmed Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
title_sort Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition
dc.creator.none.fl_str_mv Rodríguez Rodrígues, Christian Fernando Ariel
Nicolao, María Celeste
Chop, Maia
Plá, Natalia
Massaro, Mora
Loos, Julia Alexandra
Cumino, Andrea Carina
author Rodríguez Rodrígues, Christian Fernando Ariel
author_facet Rodríguez Rodrígues, Christian Fernando Ariel
Nicolao, María Celeste
Chop, Maia
Plá, Natalia
Massaro, Mora
Loos, Julia Alexandra
Cumino, Andrea Carina
author_role author
author2 Nicolao, María Celeste
Chop, Maia
Plá, Natalia
Massaro, Mora
Loos, Julia Alexandra
Cumino, Andrea Carina
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ECHINOCOCCUS GRANULOSUS
DENDRITIC CELL
T-CELL
INMUNOMODULATION
topic ECHINOCOCCUS GRANULOSUS
DENDRITIC CELL
T-CELL
INMUNOMODULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Immune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host?s response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.
Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Nicolao, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina
Fil: Chop, Maia. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Plá, Natalia. Universidad Nacional de Mar del Plata; Argentina
Fil: Massaro, Mora. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina
Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cumino, Andrea Carina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina
description Immune evasion is a hallmark of persistent echinococcal infection, comprising modulation of innate immune cells and antigen-specific T cell responses. However, recognition of Echinococcus granulosus by dendritic cells (DCs) is a key determinant of the host?s response to this parasite. Given that mTOR signaling pathway has been described as a regulator linking metabolism and immune function in DCs, we reported for the first time in these cells, global translation levels, antigen uptake, phenotype, cytokine transcriptional levels, and splenocyte priming activity upon recognition of the hydatid fluid (HF) and the highly glycosylated laminar layer (LL). We found that LL induced a slight up-regulation of CD86 and MHC II in DCs and also stimulated the production of IL-6 and TNF-α. By contrast, HF did not increase the expression of any co-stimulatory molecules, but also down-modulated CD40 and stimulated the expression of the anti-inflammatory cytokine IL-10. Both parasitic antigens promoted protein synthesis through mTOR activation. The use of rapamycin decreased the expression of the cytokines tested, empowered the down-modulation of CD40 and also reduced splenocyte proliferation. Finally, we showed that E. granulosus antigens increase the amounts of LC3-positive structures in DCs which play critical roles in the presentation of these antigens to T cells.
publishDate 2020
dc.date.none.fl_str_mv 2020-07
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/11336/230088
Rodríguez Rodrígues, Christian Fernando Ariel; Nicolao, María Celeste; Chop, Maia; Plá, Natalia; Massaro, Mora; et al.; Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition; Nature Research; Scientific Reports; 11; 1; 7-2020; 1-15
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/230088
identifier_str_mv Rodríguez Rodrígues, Christian Fernando Ariel; Nicolao, María Celeste; Chop, Maia; Plá, Natalia; Massaro, Mora; et al.; Modulation of the mTOR pathway plays a central role in dendritic cell functions after Echinococcus granulosus antigen recognition; Nature Research; Scientific Reports; 11; 1; 7-2020; 1-15
2045-2322
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.biorxiv.org/content/10.1101/2020.07.27.224055v1.abstract
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-021-96435-z
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
application/pdf
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
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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score 13.070432

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