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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Detalles Bibliográficos
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
Descripción
Sumario: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.

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