Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms

Autores
Poncini, Carolina Verónica; Ilarregui, Juan Martin; Batalla, Estela; Engels, Steef; Cerliani, Juan Pablo; Cucher, Marcela Alejandra; Van Kooyk, Yvette; González, Stella Maris; Rabinovich, Gabriel Adrián
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion. Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acute parasite infections is uncertain. In this study, we show that Gal-1 functions as a negative regulator to limit host-protective immunity following intradermal infection with Trypanosoma cruzi. Concomitant with the upregulation of immune inhibitory mediators, including IL-10, TGF-β1, IDO, and programmed death ligand 2, T. cruzi infection induced an early increase of Gal-1 expression in vivo. Compared to their wild-type (WT) counterpart, Gal-1-deficient (Lgals1-/-) mice exhibited reduced mortality and lower parasite load in muscle tissue. Resistance of Lgals1-/- mice to T. cruzi infection was associated with a failure in the activation of Gal-1-driven tolerogenic circuits, otherwise orchestrated by WT dendritic cells, leading to secondary dysfunction in the induction of CD4+CD25+Foxp3+ regulatory T cells. This effect was accompanied by an increased number of CD8+ T cells and higher frequency of IFN-γ-producing CD4+ T cells in muscle tissues and draining lymph nodes as well as reduced parasite burden in heart and hindlimb skeletal muscle. Moreover, dendritic cells lacking Gal-1 interrupted the Gal-1-mediated tolerogenic circuit and reinforced T cell-dependent anti-parasite immunity when adoptively transferred into WT mice. Thus, endogenous Gal-1 may influence T. cruzi infection by fueling tolerogenic circuits that hinder anti-parasite immunity.
Fil: Poncini, Carolina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Ilarregui, Juan Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Batalla, Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Engels, Steef. VU University Medical Cente; Países Bajos
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Van Kooyk, Yvette. VU University Medical Cente; Países Bajos
Fil: González, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Materia
Galectin-1
Trypanosoma Cruzi
Tolerogenic Circuits
Dendritic Cells
T Cells
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:11336/38780
Acceder
id CONICETDig_47d72a15ec9787dacb7a92bb9d35616a
oai_identifier_str oai:ri.conicet.gov.ar:11336/38780
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanismsPoncini, Carolina VerónicaIlarregui, Juan MartinBatalla, EstelaEngels, SteefCerliani, Juan PabloCucher, Marcela AlejandraVan Kooyk, YvetteGonzález, Stella MarisRabinovich, Gabriel AdriánGalectin-1Trypanosoma CruziTolerogenic CircuitsDendritic CellsT Cellshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion. Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acute parasite infections is uncertain. In this study, we show that Gal-1 functions as a negative regulator to limit host-protective immunity following intradermal infection with Trypanosoma cruzi. Concomitant with the upregulation of immune inhibitory mediators, including IL-10, TGF-β1, IDO, and programmed death ligand 2, T. cruzi infection induced an early increase of Gal-1 expression in vivo. Compared to their wild-type (WT) counterpart, Gal-1-deficient (Lgals1-/-) mice exhibited reduced mortality and lower parasite load in muscle tissue. Resistance of Lgals1-/- mice to T. cruzi infection was associated with a failure in the activation of Gal-1-driven tolerogenic circuits, otherwise orchestrated by WT dendritic cells, leading to secondary dysfunction in the induction of CD4+CD25+Foxp3+ regulatory T cells. This effect was accompanied by an increased number of CD8+ T cells and higher frequency of IFN-γ-producing CD4+ T cells in muscle tissues and draining lymph nodes as well as reduced parasite burden in heart and hindlimb skeletal muscle. Moreover, dendritic cells lacking Gal-1 interrupted the Gal-1-mediated tolerogenic circuit and reinforced T cell-dependent anti-parasite immunity when adoptively transferred into WT mice. Thus, endogenous Gal-1 may influence T. cruzi infection by fueling tolerogenic circuits that hinder anti-parasite immunity.Fil: Poncini, Carolina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Ilarregui, Juan Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Batalla, Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Engels, Steef. VU University Medical Cente; Países BajosFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Van Kooyk, Yvette. VU University Medical Cente; Países BajosFil: González, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaAmerican Association of Immunologists2015-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38780Poncini, Carolina Verónica; Ilarregui, Juan Martin; Batalla, Estela; Engels, Steef; Cerliani, Juan Pablo; et al.; Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms; American Association of Immunologists; Journal of Immunology; 195; 7; 10-2015; 3311-33240022-17671550-6606CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1403019info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/195/7/3311info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:16:15Zoai:ri.conicet.gov.ar:11336/38780instacron: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 15:16:15.308CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms
title Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms
spellingShingle Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms
Poncini, Carolina Verónica
Galectin-1
Trypanosoma Cruzi
Tolerogenic Circuits
Dendritic Cells
T Cells
title_short Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms
title_full Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms
title_fullStr Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms
title_full_unstemmed Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms
title_sort Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms
dc.creator.none.fl_str_mv Poncini, Carolina Verónica
Ilarregui, Juan Martin
Batalla, Estela
Engels, Steef
Cerliani, Juan Pablo
Cucher, Marcela Alejandra
Van Kooyk, Yvette
González, Stella Maris
Rabinovich, Gabriel Adrián
author Poncini, Carolina Verónica
author_facet Poncini, Carolina Verónica
Ilarregui, Juan Martin
Batalla, Estela
Engels, Steef
Cerliani, Juan Pablo
Cucher, Marcela Alejandra
Van Kooyk, Yvette
González, Stella Maris
Rabinovich, Gabriel Adrián
author_role author
author2 Ilarregui, Juan Martin
Batalla, Estela
Engels, Steef
Cerliani, Juan Pablo
Cucher, Marcela Alejandra
Van Kooyk, Yvette
González, Stella Maris
Rabinovich, Gabriel Adrián
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Galectin-1
Trypanosoma Cruzi
Tolerogenic Circuits
Dendritic Cells
T Cells
topic Galectin-1
Trypanosoma Cruzi
Tolerogenic Circuits
Dendritic Cells
T Cells
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion. Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acute parasite infections is uncertain. In this study, we show that Gal-1 functions as a negative regulator to limit host-protective immunity following intradermal infection with Trypanosoma cruzi. Concomitant with the upregulation of immune inhibitory mediators, including IL-10, TGF-β1, IDO, and programmed death ligand 2, T. cruzi infection induced an early increase of Gal-1 expression in vivo. Compared to their wild-type (WT) counterpart, Gal-1-deficient (Lgals1-/-) mice exhibited reduced mortality and lower parasite load in muscle tissue. Resistance of Lgals1-/- mice to T. cruzi infection was associated with a failure in the activation of Gal-1-driven tolerogenic circuits, otherwise orchestrated by WT dendritic cells, leading to secondary dysfunction in the induction of CD4+CD25+Foxp3+ regulatory T cells. This effect was accompanied by an increased number of CD8+ T cells and higher frequency of IFN-γ-producing CD4+ T cells in muscle tissues and draining lymph nodes as well as reduced parasite burden in heart and hindlimb skeletal muscle. Moreover, dendritic cells lacking Gal-1 interrupted the Gal-1-mediated tolerogenic circuit and reinforced T cell-dependent anti-parasite immunity when adoptively transferred into WT mice. Thus, endogenous Gal-1 may influence T. cruzi infection by fueling tolerogenic circuits that hinder anti-parasite immunity.
Fil: Poncini, Carolina Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Ilarregui, Juan Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Batalla, Estela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Engels, Steef. VU University Medical Cente; Países Bajos
Fil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Van Kooyk, Yvette. VU University Medical Cente; Países Bajos
Fil: González, Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina
Fil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
description Galectin-1 (Gal-1), an endogenous glycan-binding protein, is widely distributed at sites of inflammation and microbial invasion. Despite considerable progress regarding the immunoregulatory activity of this lectin, the role of endogenous Gal-1 during acute parasite infections is uncertain. In this study, we show that Gal-1 functions as a negative regulator to limit host-protective immunity following intradermal infection with Trypanosoma cruzi. Concomitant with the upregulation of immune inhibitory mediators, including IL-10, TGF-β1, IDO, and programmed death ligand 2, T. cruzi infection induced an early increase of Gal-1 expression in vivo. Compared to their wild-type (WT) counterpart, Gal-1-deficient (Lgals1-/-) mice exhibited reduced mortality and lower parasite load in muscle tissue. Resistance of Lgals1-/- mice to T. cruzi infection was associated with a failure in the activation of Gal-1-driven tolerogenic circuits, otherwise orchestrated by WT dendritic cells, leading to secondary dysfunction in the induction of CD4+CD25+Foxp3+ regulatory T cells. This effect was accompanied by an increased number of CD8+ T cells and higher frequency of IFN-γ-producing CD4+ T cells in muscle tissues and draining lymph nodes as well as reduced parasite burden in heart and hindlimb skeletal muscle. Moreover, dendritic cells lacking Gal-1 interrupted the Gal-1-mediated tolerogenic circuit and reinforced T cell-dependent anti-parasite immunity when adoptively transferred into WT mice. Thus, endogenous Gal-1 may influence T. cruzi infection by fueling tolerogenic circuits that hinder anti-parasite immunity.
publishDate 2015
dc.date.none.fl_str_mv 2015-10
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/11336/38780
Poncini, Carolina Verónica; Ilarregui, Juan Martin; Batalla, Estela; Engels, Steef; Cerliani, Juan Pablo; et al.; Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms; American Association of Immunologists; Journal of Immunology; 195; 7; 10-2015; 3311-3324
0022-1767
1550-6606
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38780
identifier_str_mv Poncini, Carolina Verónica; Ilarregui, Juan Martin; Batalla, Estela; Engels, Steef; Cerliani, Juan Pablo; et al.; Trypanosoma cruzi infection imparts a regulatory program in dendritic cells and T cells via galectin-1-dependent mechanisms; American Association of Immunologists; Journal of Immunology; 195; 7; 10-2015; 3311-3324
0022-1767
1550-6606
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1403019
info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/195/7/3311
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
dc.publisher.none.fl_str_mv American Association of Immunologists
publisher.none.fl_str_mv American Association of Immunologists
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 13.22299

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