Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment

Autores
González, Florencia Belén; Calmon Hamaty, Flavia; Nô Seara Cordeiro, Synara; Fernandez Bussy, Rodrigo; Spinelli, Silvana Virginia; D'attilio, Luciano David; Bottasso, Oscar Adelmo; Savino, Wilson; Cotta de Almeida, Vinícius; Villar, Silvina Raquel; Perez, Ana Rosa
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The dynamics of regulatory T cells in the course of Trypanosoma cruzi infection is still debated. We previously demonstrated that acute murine T. cruzi infection results in an impaired peripheral CD4+Foxp3+ T cell differentiation due to the acquisition of an abnormal Th1-like phenotype and altered functional features, negatively impacting on the course of infection. Moreover, T. cruzi infection induces an intense thymic atrophy. As known, the thymus is the primary lymphoid organ in which thymic-derived regulatory T cells, known as tTregs, differentiate. Considering the lack of available data about the effect of T. cruzi infection upon tTregs, we examined tTreg dynamics during the course of disease. We confirmed that T. cruzi infection induces a marked loss of tTreg cell number associated to cell precursor exhaustion, partially avoided by glucocorticoid ablation- and IL-2 survival factor depletion. At the same time, tTregs accumulate within the CD4 single-positive compartment, exhibiting an increased Ki-67/Annexin V ratio compared to controls. Moreover, tTregs enhance after the infection the expression of signature markers (CD25, CD62L and GITR) and they also display alterations in the expression of migration-associated molecules (α chains of VLAs and chemokine receptors) such as functional fibronectin-driven migratory disturbance. Taken together, we provide data demonstrating profound alterations in tTreg compartment during acute murine T. cruzi infection, denoting that their homeostasis is significantly affected. The evident loss of tTreg cell number may compromise the composition of tTreg peripheral pool, and such sustained alteration over time may be partially related to the immune dysregulation observed in the chronic phase of the disease.
Fil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Calmon Hamaty, Flavia. Fundación Oswaldo Cruz; Brasil
Fil: Nô Seara Cordeiro, Synara. Fundación Oswaldo Cruz; Brasil
Fil: Fernandez Bussy, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Spinelli, Silvana Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: D'attilio, Luciano David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Savino, Wilson. Fundación Oswaldo Cruz; Brasil
Fil: Cotta de Almeida, Vinícius. Fundación Oswaldo Cruz; Brasil
Fil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Perez, Ana Rosa. Fiocruz - Laboratorio de Pesquisas Sobre O Timo; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Materia
Chagas disease
Interleukin-2
Foxp3 cells
Thymus
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:11336/100785
Acceder
id CONICETDig_a2742da734a8d5100df20a8180643ad7
oai_identifier_str oai:ri.conicet.gov.ar:11336/100785
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell CompartmentGonzález, Florencia BelénCalmon Hamaty, FlaviaNô Seara Cordeiro, SynaraFernandez Bussy, RodrigoSpinelli, Silvana VirginiaD'attilio, Luciano DavidBottasso, Oscar AdelmoSavino, WilsonCotta de Almeida, ViníciusVillar, Silvina RaquelPerez, Ana RosaChagas diseaseInterleukin-2Foxp3 cellsThymushttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The dynamics of regulatory T cells in the course of Trypanosoma cruzi infection is still debated. We previously demonstrated that acute murine T. cruzi infection results in an impaired peripheral CD4+Foxp3+ T cell differentiation due to the acquisition of an abnormal Th1-like phenotype and altered functional features, negatively impacting on the course of infection. Moreover, T. cruzi infection induces an intense thymic atrophy. As known, the thymus is the primary lymphoid organ in which thymic-derived regulatory T cells, known as tTregs, differentiate. Considering the lack of available data about the effect of T. cruzi infection upon tTregs, we examined tTreg dynamics during the course of disease. We confirmed that T. cruzi infection induces a marked loss of tTreg cell number associated to cell precursor exhaustion, partially avoided by glucocorticoid ablation- and IL-2 survival factor depletion. At the same time, tTregs accumulate within the CD4 single-positive compartment, exhibiting an increased Ki-67/Annexin V ratio compared to controls. Moreover, tTregs enhance after the infection the expression of signature markers (CD25, CD62L and GITR) and they also display alterations in the expression of migration-associated molecules (α chains of VLAs and chemokine receptors) such as functional fibronectin-driven migratory disturbance. Taken together, we provide data demonstrating profound alterations in tTreg compartment during acute murine T. cruzi infection, denoting that their homeostasis is significantly affected. The evident loss of tTreg cell number may compromise the composition of tTreg peripheral pool, and such sustained alteration over time may be partially related to the immune dysregulation observed in the chronic phase of the disease.Fil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Calmon Hamaty, Flavia. Fundación Oswaldo Cruz; BrasilFil: Nô Seara Cordeiro, Synara. Fundación Oswaldo Cruz; BrasilFil: Fernandez Bussy, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Spinelli, Silvana Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: D'attilio, Luciano David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Savino, Wilson. Fundación Oswaldo Cruz; BrasilFil: Cotta de Almeida, Vinícius. Fundación Oswaldo Cruz; BrasilFil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Perez, Ana Rosa. Fiocruz - Laboratorio de Pesquisas Sobre O Timo; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaPublic Library of Science2016-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/100785González, Florencia Belén; Calmon Hamaty, Flavia; Nô Seara Cordeiro, Synara; Fernandez Bussy, Rodrigo; Spinelli, Silvana Virginia; et al.; Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment; Public Library of Science; Neglected Tropical Diseases; 10; 1; 1-2016; 1-211935-2735CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0004285info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004285info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:02Zoai:ri.conicet.gov.ar:11336/100785instacron: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 09:47:02.652CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
title Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
spellingShingle Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
González, Florencia Belén
Chagas disease
Interleukin-2
Foxp3 cells
Thymus
title_short Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
title_full Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
title_fullStr Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
title_full_unstemmed Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
title_sort Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment
dc.creator.none.fl_str_mv González, Florencia Belén
Calmon Hamaty, Flavia
Nô Seara Cordeiro, Synara
Fernandez Bussy, Rodrigo
Spinelli, Silvana Virginia
D'attilio, Luciano David
Bottasso, Oscar Adelmo
Savino, Wilson
Cotta de Almeida, Vinícius
Villar, Silvina Raquel
Perez, Ana Rosa
author González, Florencia Belén
author_facet González, Florencia Belén
Calmon Hamaty, Flavia
Nô Seara Cordeiro, Synara
Fernandez Bussy, Rodrigo
Spinelli, Silvana Virginia
D'attilio, Luciano David
Bottasso, Oscar Adelmo
Savino, Wilson
Cotta de Almeida, Vinícius
Villar, Silvina Raquel
Perez, Ana Rosa
author_role author
author2 Calmon Hamaty, Flavia
Nô Seara Cordeiro, Synara
Fernandez Bussy, Rodrigo
Spinelli, Silvana Virginia
D'attilio, Luciano David
Bottasso, Oscar Adelmo
Savino, Wilson
Cotta de Almeida, Vinícius
Villar, Silvina Raquel
Perez, Ana Rosa
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Chagas disease
Interleukin-2
Foxp3 cells
Thymus
topic Chagas disease
Interleukin-2
Foxp3 cells
Thymus
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv The dynamics of regulatory T cells in the course of Trypanosoma cruzi infection is still debated. We previously demonstrated that acute murine T. cruzi infection results in an impaired peripheral CD4+Foxp3+ T cell differentiation due to the acquisition of an abnormal Th1-like phenotype and altered functional features, negatively impacting on the course of infection. Moreover, T. cruzi infection induces an intense thymic atrophy. As known, the thymus is the primary lymphoid organ in which thymic-derived regulatory T cells, known as tTregs, differentiate. Considering the lack of available data about the effect of T. cruzi infection upon tTregs, we examined tTreg dynamics during the course of disease. We confirmed that T. cruzi infection induces a marked loss of tTreg cell number associated to cell precursor exhaustion, partially avoided by glucocorticoid ablation- and IL-2 survival factor depletion. At the same time, tTregs accumulate within the CD4 single-positive compartment, exhibiting an increased Ki-67/Annexin V ratio compared to controls. Moreover, tTregs enhance after the infection the expression of signature markers (CD25, CD62L and GITR) and they also display alterations in the expression of migration-associated molecules (α chains of VLAs and chemokine receptors) such as functional fibronectin-driven migratory disturbance. Taken together, we provide data demonstrating profound alterations in tTreg compartment during acute murine T. cruzi infection, denoting that their homeostasis is significantly affected. The evident loss of tTreg cell number may compromise the composition of tTreg peripheral pool, and such sustained alteration over time may be partially related to the immune dysregulation observed in the chronic phase of the disease.
Fil: González, Florencia Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Calmon Hamaty, Flavia. Fundación Oswaldo Cruz; Brasil
Fil: Nô Seara Cordeiro, Synara. Fundación Oswaldo Cruz; Brasil
Fil: Fernandez Bussy, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Spinelli, Silvana Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: D'attilio, Luciano David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Savino, Wilson. Fundación Oswaldo Cruz; Brasil
Fil: Cotta de Almeida, Vinícius. Fundación Oswaldo Cruz; Brasil
Fil: Villar, Silvina Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
Fil: Perez, Ana Rosa. Fiocruz - Laboratorio de Pesquisas Sobre O Timo; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina
description The dynamics of regulatory T cells in the course of Trypanosoma cruzi infection is still debated. We previously demonstrated that acute murine T. cruzi infection results in an impaired peripheral CD4+Foxp3+ T cell differentiation due to the acquisition of an abnormal Th1-like phenotype and altered functional features, negatively impacting on the course of infection. Moreover, T. cruzi infection induces an intense thymic atrophy. As known, the thymus is the primary lymphoid organ in which thymic-derived regulatory T cells, known as tTregs, differentiate. Considering the lack of available data about the effect of T. cruzi infection upon tTregs, we examined tTreg dynamics during the course of disease. We confirmed that T. cruzi infection induces a marked loss of tTreg cell number associated to cell precursor exhaustion, partially avoided by glucocorticoid ablation- and IL-2 survival factor depletion. At the same time, tTregs accumulate within the CD4 single-positive compartment, exhibiting an increased Ki-67/Annexin V ratio compared to controls. Moreover, tTregs enhance after the infection the expression of signature markers (CD25, CD62L and GITR) and they also display alterations in the expression of migration-associated molecules (α chains of VLAs and chemokine receptors) such as functional fibronectin-driven migratory disturbance. Taken together, we provide data demonstrating profound alterations in tTreg compartment during acute murine T. cruzi infection, denoting that their homeostasis is significantly affected. The evident loss of tTreg cell number may compromise the composition of tTreg peripheral pool, and such sustained alteration over time may be partially related to the immune dysregulation observed in the chronic phase of the disease.
publishDate 2016
dc.date.none.fl_str_mv 2016-01
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/11336/100785
González, Florencia Belén; Calmon Hamaty, Flavia; Nô Seara Cordeiro, Synara; Fernandez Bussy, Rodrigo; Spinelli, Silvana Virginia; et al.; Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment; Public Library of Science; Neglected Tropical Diseases; 10; 1; 1-2016; 1-21
1935-2735
CONICET Digital
CONICET
url http://hdl.handle.net/11336/100785
identifier_str_mv González, Florencia Belén; Calmon Hamaty, Flavia; Nô Seara Cordeiro, Synara; Fernandez Bussy, Rodrigo; Spinelli, Silvana Virginia; et al.; Trypanosoma cruzi Experimental Infection Impacts on the Thymic Regulatory T Cell Compartment; Public Library of Science; Neglected Tropical Diseases; 10; 1; 1-2016; 1-21
1935-2735
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0004285
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004285
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
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
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reponame_str CONICET Digital (CONICET)
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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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