Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease

Autores
Lepletier, Ailin; de Almeida, Liliane; Santos, Leonardo; da Silva Sampaio, Luzia; Paredes, Bruno; González, Florencia Belén; Freire de Lima, Celio Geraldo; Beloscar, Juan; Bottasso, Oscar Adelmo; Einicker Lamas, Marcelo; Perez, Ana Rosa; Savino, Wilson; Morrot, Alexandre
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironmental and lymphoid compartments. Acute infection results in severe atrophy of the organ and early release of immature thymocytes into the periphery. To date, the pathophysiological effects of thymic changes promoted by parasite-inducing premature release of thymocytes to the periphery has remained elusive. Herein, we show that sphingosine-1-phosphate (S1P), a potent mediator of T cell chemotaxis, plays a role in the exit of immature double-negative thymocytes in experimental Chagas disease. In thymuses from T. cruzi-infected mice we detected reduced transcription of the S1P kinase 1 and 2 genes related to S1P biosynthesis, together with increased transcription of the SGPL1 sphingosine-1-lyase gene, whose product inactivates S1P. These changes were associated with reduced intrathymic levels of S1P kinase activity. Interestingly, double-negative thymocytes from infected animals expressed high levels of the S1P receptor during infection, and migrated to lower levels of S1P. Moreover, during T. cruzi infection, this thymocyte subset expresses high levels of IL-17 and TNF-α cytokines upon polyclonal stimulation. In vivo treatment with the S1P receptor antagonist FTY720 resulted in recovery the numbers of double-negative thymocytes in infected thymuses to physiological levels. Finally, we showed increased numbers of double-negative T cells in the peripheral blood in severe cardiac forms of human Chagas disease.
Fil: Lepletier, Ailin. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
Fil: de Almeida, Liliane. Universidade Federal do Rio de Janeiro; Brasil
Fil: Santos, Leonardo. Universidade Federal do Rio de Janeiro; Brasil
Fil: da Silva Sampaio, Luzia. Universidade Federal do Rio de Janeiro; Brasil
Fil: Paredes, Bruno. Universidade Federal do Rio de Janeiro; Brasil
Fil: González, Florencia Belén. Universidad Nacional de Rosario; Argentina
Fil: Freire de Lima, Celio Geraldo. Universidade Federal do Rio de Janeiro; Brasil
Fil: Beloscar, Juan. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; Argentina
Fil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; Argentina
Fil: Einicker Lamas, Marcelo. Universidade Federal do Rio de Janeiro; Brasil
Fil: Perez, Ana Rosa. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Savino, Wilson. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
Fil: Morrot, Alexandre. Universidade Federal do Rio de Janeiro; Brasil
Materia
double negative cells
Chagas disease
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:11336/31051
Acceder
id CONICETDig_52fe3995902a9ccf16dd2a25153085ae
oai_identifier_str oai:ri.conicet.gov.ar:11336/31051
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas DiseaseLepletier, Ailinde Almeida, LilianeSantos, Leonardoda Silva Sampaio, LuziaParedes, BrunoGonzález, Florencia BelénFreire de Lima, Celio GeraldoBeloscar, JuanBottasso, Oscar AdelmoEinicker Lamas, MarceloPerez, Ana RosaSavino, WilsonMorrot, Alexandredouble negative cellsChagas diseasethymushttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3The protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironmental and lymphoid compartments. Acute infection results in severe atrophy of the organ and early release of immature thymocytes into the periphery. To date, the pathophysiological effects of thymic changes promoted by parasite-inducing premature release of thymocytes to the periphery has remained elusive. Herein, we show that sphingosine-1-phosphate (S1P), a potent mediator of T cell chemotaxis, plays a role in the exit of immature double-negative thymocytes in experimental Chagas disease. In thymuses from T. cruzi-infected mice we detected reduced transcription of the S1P kinase 1 and 2 genes related to S1P biosynthesis, together with increased transcription of the SGPL1 sphingosine-1-lyase gene, whose product inactivates S1P. These changes were associated with reduced intrathymic levels of S1P kinase activity. Interestingly, double-negative thymocytes from infected animals expressed high levels of the S1P receptor during infection, and migrated to lower levels of S1P. Moreover, during T. cruzi infection, this thymocyte subset expresses high levels of IL-17 and TNF-α cytokines upon polyclonal stimulation. In vivo treatment with the S1P receptor antagonist FTY720 resulted in recovery the numbers of double-negative thymocytes in infected thymuses to physiological levels. Finally, we showed increased numbers of double-negative T cells in the peripheral blood in severe cardiac forms of human Chagas disease.Fil: Lepletier, Ailin. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; BrasilFil: de Almeida, Liliane. Universidade Federal do Rio de Janeiro; BrasilFil: Santos, Leonardo. Universidade Federal do Rio de Janeiro; BrasilFil: da Silva Sampaio, Luzia. Universidade Federal do Rio de Janeiro; BrasilFil: Paredes, Bruno. Universidade Federal do Rio de Janeiro; BrasilFil: González, Florencia Belén. Universidad Nacional de Rosario; ArgentinaFil: Freire de Lima, Celio Geraldo. Universidade Federal do Rio de Janeiro; BrasilFil: Beloscar, Juan. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; ArgentinaFil: Einicker Lamas, Marcelo. Universidade Federal do Rio de Janeiro; BrasilFil: Perez, Ana Rosa. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Savino, Wilson. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; BrasilFil: Morrot, Alexandre. Universidade Federal do Rio de Janeiro; BrasilPublic Library of Science2014-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/31051Morrot, Alexandre; Savino, Wilson; Perez, Ana Rosa; Einicker Lamas, Marcelo; Bottasso, Oscar Adelmo; Beloscar, Juan; et al.; Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease; Public Library of Science; Neglected Tropical Diseases; 8; e320; 9-2014; 1-141935-2735CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pntd.0003203info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003203info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:18:12Zoai:ri.conicet.gov.ar:11336/31051instacron: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:34982025-10-22 12:18:12.386CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease
title Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease
spellingShingle Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease
Lepletier, Ailin
double negative cells
Chagas disease
thymus
title_short Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease
title_full Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease
title_fullStr Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease
title_full_unstemmed Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease
title_sort Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease
dc.creator.none.fl_str_mv Lepletier, Ailin
de Almeida, Liliane
Santos, Leonardo
da Silva Sampaio, Luzia
Paredes, Bruno
González, Florencia Belén
Freire de Lima, Celio Geraldo
Beloscar, Juan
Bottasso, Oscar Adelmo
Einicker Lamas, Marcelo
Perez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author Lepletier, Ailin
author_facet Lepletier, Ailin
de Almeida, Liliane
Santos, Leonardo
da Silva Sampaio, Luzia
Paredes, Bruno
González, Florencia Belén
Freire de Lima, Celio Geraldo
Beloscar, Juan
Bottasso, Oscar Adelmo
Einicker Lamas, Marcelo
Perez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author_role author
author2 de Almeida, Liliane
Santos, Leonardo
da Silva Sampaio, Luzia
Paredes, Bruno
González, Florencia Belén
Freire de Lima, Celio Geraldo
Beloscar, Juan
Bottasso, Oscar Adelmo
Einicker Lamas, Marcelo
Perez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv double negative cells
Chagas disease
thymus
topic double negative cells
Chagas disease
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 protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironmental and lymphoid compartments. Acute infection results in severe atrophy of the organ and early release of immature thymocytes into the periphery. To date, the pathophysiological effects of thymic changes promoted by parasite-inducing premature release of thymocytes to the periphery has remained elusive. Herein, we show that sphingosine-1-phosphate (S1P), a potent mediator of T cell chemotaxis, plays a role in the exit of immature double-negative thymocytes in experimental Chagas disease. In thymuses from T. cruzi-infected mice we detected reduced transcription of the S1P kinase 1 and 2 genes related to S1P biosynthesis, together with increased transcription of the SGPL1 sphingosine-1-lyase gene, whose product inactivates S1P. These changes were associated with reduced intrathymic levels of S1P kinase activity. Interestingly, double-negative thymocytes from infected animals expressed high levels of the S1P receptor during infection, and migrated to lower levels of S1P. Moreover, during T. cruzi infection, this thymocyte subset expresses high levels of IL-17 and TNF-α cytokines upon polyclonal stimulation. In vivo treatment with the S1P receptor antagonist FTY720 resulted in recovery the numbers of double-negative thymocytes in infected thymuses to physiological levels. Finally, we showed increased numbers of double-negative T cells in the peripheral blood in severe cardiac forms of human Chagas disease.
Fil: Lepletier, Ailin. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
Fil: de Almeida, Liliane. Universidade Federal do Rio de Janeiro; Brasil
Fil: Santos, Leonardo. Universidade Federal do Rio de Janeiro; Brasil
Fil: da Silva Sampaio, Luzia. Universidade Federal do Rio de Janeiro; Brasil
Fil: Paredes, Bruno. Universidade Federal do Rio de Janeiro; Brasil
Fil: González, Florencia Belén. Universidad Nacional de Rosario; Argentina
Fil: Freire de Lima, Celio Geraldo. Universidade Federal do Rio de Janeiro; Brasil
Fil: Beloscar, Juan. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; Argentina
Fil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; Argentina
Fil: Einicker Lamas, Marcelo. Universidade Federal do Rio de Janeiro; Brasil
Fil: Perez, Ana Rosa. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Savino, Wilson. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
Fil: Morrot, Alexandre. Universidade Federal do Rio de Janeiro; Brasil
description The protozoan parasite Trypanosoma cruzi is able to target the thymus and induce alterations of the thymic microenvironmental and lymphoid compartments. Acute infection results in severe atrophy of the organ and early release of immature thymocytes into the periphery. To date, the pathophysiological effects of thymic changes promoted by parasite-inducing premature release of thymocytes to the periphery has remained elusive. Herein, we show that sphingosine-1-phosphate (S1P), a potent mediator of T cell chemotaxis, plays a role in the exit of immature double-negative thymocytes in experimental Chagas disease. In thymuses from T. cruzi-infected mice we detected reduced transcription of the S1P kinase 1 and 2 genes related to S1P biosynthesis, together with increased transcription of the SGPL1 sphingosine-1-lyase gene, whose product inactivates S1P. These changes were associated with reduced intrathymic levels of S1P kinase activity. Interestingly, double-negative thymocytes from infected animals expressed high levels of the S1P receptor during infection, and migrated to lower levels of S1P. Moreover, during T. cruzi infection, this thymocyte subset expresses high levels of IL-17 and TNF-α cytokines upon polyclonal stimulation. In vivo treatment with the S1P receptor antagonist FTY720 resulted in recovery the numbers of double-negative thymocytes in infected thymuses to physiological levels. Finally, we showed increased numbers of double-negative T cells in the peripheral blood in severe cardiac forms of human Chagas disease.
publishDate 2014
dc.date.none.fl_str_mv 2014-09
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/11336/31051
Morrot, Alexandre; Savino, Wilson; Perez, Ana Rosa; Einicker Lamas, Marcelo; Bottasso, Oscar Adelmo; Beloscar, Juan; et al.; Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease; Public Library of Science; Neglected Tropical Diseases; 8; e320; 9-2014; 1-14
1935-2735
CONICET Digital
CONICET
url http://hdl.handle.net/11336/31051
identifier_str_mv Morrot, Alexandre; Savino, Wilson; Perez, Ana Rosa; Einicker Lamas, Marcelo; Bottasso, Oscar Adelmo; Beloscar, Juan; et al.; Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease; Public Library of Science; Neglected Tropical Diseases; 8; e320; 9-2014; 1-14
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.0003203
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0003203
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
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)
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 12.982451

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