Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.

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...

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Autores principales: Lepletier, Ailin, de Almeida, Liliane, Santos, Leonardo, da Silva Sampaio, Luzia, Paredes, Bruno, González, Florencia Belén, Freire-de-Lima, Célio Geraldo, Beloscar, Juan, Bottasso, Oscar, Einicker-Lamas, Marcelo, Pérez, Ana Rosa, Savino, Wilson, Morrot, Alexandre
Formato: article artículo publishedVersion
Lenguaje:Inglés
Publicado: PLOS (Public Library of Science) 2015
Materias:
Chagas desease
Flow cytometry
Atrophy
T cell receptors
T cell
Thymocytes
Trypanosoma cruzi
Acceso en línea:http://hdl.handle.net/2133/4924
http://hdl.handle.net/2133/4924
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-4924
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Chagas desease
Flow cytometry
Atrophy
T cell receptors
T cell
Thymocytes
Trypanosoma cruzi
spellingShingle Chagas desease
Flow cytometry
Atrophy
T cell receptors
T cell
Thymocytes
Trypanosoma cruzi
Lepletier, Ailin
de Almeida, Liliane
Santos, Leonardo
da Silva Sampaio, Luzia
Paredes, Bruno
González, Florencia Belén
Freire-de-Lima, Célio Geraldo
Beloscar, Juan
Bottasso, Oscar
Einicker-Lamas, Marcelo
Pérez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.
topic_facet Chagas desease
Flow cytometry
Atrophy
T cell receptors
T cell
Thymocytes
Trypanosoma cruzi
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.
format article
artículo
publishedVersion
author Lepletier, Ailin
de Almeida, Liliane
Santos, Leonardo
da Silva Sampaio, Luzia
Paredes, Bruno
González, Florencia Belén
Freire-de-Lima, Célio Geraldo
Beloscar, Juan
Bottasso, Oscar
Einicker-Lamas, Marcelo
Pérez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author_facet Lepletier, Ailin
de Almeida, Liliane
Santos, Leonardo
da Silva Sampaio, Luzia
Paredes, Bruno
González, Florencia Belén
Freire-de-Lima, Célio Geraldo
Beloscar, Juan
Bottasso, Oscar
Einicker-Lamas, Marcelo
Pérez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
author_sort Lepletier, Ailin
title Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.
title_short Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.
title_full Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.
title_fullStr Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.
title_full_unstemmed Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.
title_sort early double-negative thymocyte export in trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.
publisher PLOS (Public Library of Science)
publishDate 2015
url http://hdl.handle.net/2133/4924
http://hdl.handle.net/2133/4924
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