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

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dc.creator Lepletier, Ailin
dc.creator de Almeida, Liliane
dc.creator Santos, Leonardo
dc.creator da Silva Sampaio, Luzia
dc.creator Paredes, Bruno
dc.creator González, Florencia Belén
dc.creator Freire-de-Lima, Célio Geraldo
dc.creator Beloscar, Juan
dc.creator Bottasso, Oscar
dc.creator Einicker-Lamas, Marcelo
dc.creator Pérez, Ana Rosa
dc.creator Savino, Wilson
dc.creator Morrot, Alexandre
dc.date.accessioned 2015-08-21T14:12:58Z
dc.date.available 2015-08-21T14:12:58Z
dc.date.issued 2014-10-16
dc.identifier.issn 1935-2735 es
dc.identifier.uri http://hdl.handle.net/2133/4924
dc.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. es
dc.format application/pdf
dc.format.extent 1-14 es
dc.language.iso eng es
dc.publisher PLOS (Public Library of Science) es
dc.rights openAccess es
dc.rights.uri http://creativecommons.org/licenses/by/2.5/ar/ *
dc.subject Chagas desease es
dc.subject Flow cytometry es
dc.subject Atrophy es
dc.subject T cell receptors es
dc.subject T cell es
dc.subject Thymocytes es
dc.subject Trypanosoma cruzi es
dc.title Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease. es
dc.type article
dc.type artículo
dc.type publishedVersion
dc.rights.holder 2014 Lepletier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. es
dc.relation.publisherversion doi:10.1371/journal.pntd.0003203 es
dc.rights.text Creative Commons Attribution (CC BY) es
dc.citation.title PLOS Neglected Tropical Diseases es
dc.description.fil Fil: Lepletier, Ailin. Laboratory on Thymus Research, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil es
dc.description.fil Fil: de Almeida, Liliane. Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil es
dc.type.collection articulo
dc.type.version publishedVersion es


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