Early Double-Negative Thymocyte Export inTrypanosoma cruziInfection Is Restricted by SphingosineReceptors and Associated with Human Chagas Disease

Authors
Lepletier, Ailin; de Almeida, Liliane; Santos, Leonardo; da Silva Sampaio, Luzia; Paredes, Bruno; González, Florencia Belén; Freire de Lima, Celio Geraldo; Beloscar, Juan; Bottasso, Oscar Adelmo; Einicker Lamas, Marcelo; Perez, Ana Rosa; Savino, Wilson; Morrot, Alexandre
Publication Year
2014
Language
English
Format
article
Status
Published version
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.
Fil: Lepletier, Ailin. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
Fil: de Almeida, Liliane. Universidade Federal do Rio de Janeiro; Brasil
Fil: Santos, Leonardo. Universidade Federal do Rio de Janeiro; Brasil
Fil: da Silva Sampaio, Luzia. Universidade Federal do Rio de Janeiro; Brasil
Fil: Paredes, Bruno. Universidade Federal do Rio de Janeiro; Brasil
Fil: González, Florencia Belén. Universidad Nacional de Rosario; Argentina
Fil: Freire de Lima, Celio Geraldo. Universidade Federal do Rio de Janeiro; Brasil
Fil: Beloscar, Juan. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; Argentina
Fil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Santa Fe. Ministerio de Salud. Hospital J. B. Iturraspe; Argentina
Fil: Einicker Lamas, Marcelo. Universidade Federal do Rio de Janeiro; Brasil
Fil: Perez, Ana Rosa. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Savino, Wilson. Escola Nacional de Saude Publica Sergio Arouca. Fundación Oswaldo Cruz; Brasil
Fil: Morrot, Alexandre. Universidade Federal do Rio de Janeiro; Brasil
Subject
double negative cells
Chagas disease
thymus
Inmunología
Medicina Básica
CIENCIAS MÉDICAS Y DE LA SALUD
Access level
Open access
License
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repository
CONICET Digital (CONICET)
Institution
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identifier
oai:ri.conicet.gov.ar:11336/31051