Author | Lepletier, Ailin | |
Author | Almeida, Liliane de | |
Author | Santos, Leonardo | |
Author | Sampaio, Luzia da Silva | |
Author | Paredes, Bruno | |
Author | González, Florencia Belén | |
Author | Lima, Célio Geraldo Freire de | |
Author | Beloscar, Juan | |
Author | Botasso, Oscar | |
Author | Lamas, Marcelo Einicker | |
Author | Pérez, Ana Rosa | |
Author | Savino, Wilson | |
Author | Morrot, Alexandre | |
Access date | 2015-06-08T14:01:48Z | |
Available date | 2015-06-08T14:01:48Z | |
Document date | 2014 | pt_BR |
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. | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/10684 | |
Language | eng | pt_BR |
Publisher | Plos One | pt_BR |
Rights | open access | pt_BR |
Title | Early Double-Negative Thymocyte Export in Trypanosoma cruzi Infection Is Restricted by Sphingosine Receptors and Associated with Human Chagas Disease | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.pntd.0003203 | pt_BR |
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. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | National University of Rosario. Institute of Immunology. Rosario, Argentina. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Hospital J.B. Iturraspe. Servicio de Clínica Médica. Santa Fé, Argentina. | pt_BR |
Affilliation | Hospital J.B. Iturraspe. Servicio de Clínica Médica. Santa Fé, Argentina. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | National University of Rosario. Institute of Immunology. Rosario, Argentina. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa sobre o Timo. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Chagas Disease | pt_BR |
Subject | Sphingosine Receptors | pt_BR |
DeCS | Trypanosoma cruzi | pt_BR |
DeCS | Doença de Chagas | pt_BR |
DeCS | Psicosina | pt_BR |