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

dc.citation.titlePLOS Neglected Tropical Diseaseses
dc.creatorLepletier, Ailin
dc.creatorde Almeida, Liliane
dc.creatorSantos, Leonardo
dc.creatorda Silva Sampaio, Luzia
dc.creatorParedes, Bruno
dc.creatorGonzález, Florencia Belén
dc.creatorFreire-de-Lima, Célio Geraldo
dc.creatorBeloscar, Juan
dc.creatorBottasso, Oscar
dc.creatorEinicker-Lamas, Marcelo
dc.creatorPérez, Ana Rosa
dc.creatorSavino, Wilson
dc.creatorMorrot, Alexandre
dc.date.accessioned2015-08-21T14:12:58Z
dc.date.available2015-08-21T14:12:58Z
dc.date.issued2014-10-16
dc.descriptionThe 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.description.filFil: Lepletier, Ailin. Laboratory on Thymus Research, Oswaldo Cruz Foundation, Rio de Janeiro, Braziles
dc.description.filFil: de Almeida, Liliane. Institute of Microbiology, Federal University of Rio de Janeiro, Rio de Janeiro, Braziles
dc.formatapplication/pdf
dc.format.extent1-14es
dc.identifier.issn1935-2735es
dc.identifier.urihttp://hdl.handle.net/2133/4924
dc.language.isoenges
dc.publisherPLOS (Public Library of Science)es
dc.relation.publisherversiondoi:10.1371/journal.pntd.0003203es
dc.rightsopenAccesses
dc.rights.holder2014 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.rights.textCreative Commons Attribution (CC BY)es
dc.rights.urihttp://creativecommons.org/licenses/by/2.5/ar/*
dc.subjectChagas deseasees
dc.subjectFlow cytometryes
dc.subjectAtrophyes
dc.subjectT cell receptorses
dc.subjectT celles
dc.subjectThymocyteses
dc.subjectTrypanosoma cruzies
dc.titleEarly double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.es
dc.typearticle
dc.typeartículo
dc.typepublishedVersion
dc.type.collectionarticulo
dc.type.versionpublishedVersiones

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