Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/10684
Title: Early Double-Negative Thymocyte Export in Trypanosoma cruzi Infection Is Restricted by Sphingosine Receptors and Associated with Human Chagas Disease
Authors: Lepletier, Ailin
Almeida, Liliane de
Santos, Leonardo
Sampaio, Luzia da Silva
Paredes, Bruno
González, Florencia Belén
Lima, Célio Geraldo Freire de
Beloscar, Juan
Botasso, Oscar
Lamas, Marcelo Einicker
Pérez, Ana Rosa
Savino, Wilson
Morrot, Alexandre
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
National University of Rosario. Institute of Immunology. Rosario, Argentina.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
Hospital J.B. Iturraspe. Servicio de Clínica Médica. Santa Fé, Argentina.
Hospital J.B. Iturraspe. Servicio de Clínica Médica. Santa Fé, Argentina.
Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil.
National University of Rosario. Institute of Immunology. Rosario, Argentina.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil.
Abstract: 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-a 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.
Keywords: Trypanosoma cruzi
Chagas Disease
Sphingosine Receptors
DeCS: Trypanosoma cruzi
Doença de Chagas
Psicosina
Issue Date: 2014
Publisher: Plos One
Citation: LEPLETIER, Ailin et al. Early Double-Negative Thymocyte Export in Trypanosoma cruzi Infection Is Restricted by Sphingosine Receptors and Associated with Human Chagas Disease. PLOS Neglected Tropical Diseases, v.8, n.10, 14p, oct. 2014.
DOI: 10.1371/journal.pntd.0003203
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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