Modulation of Intrathymic Sphingosine-1-Phosphate Levels Promotes Escape of Immature Thymocytes to the Periphery with a Potential Proinflammatory Role in Chagas Disease.
The sphingosine-1-phosphate (S1P) system regulates both thymic and lymph nodes T cell egress which is essential for producing and maintaining the recycling T cell repertoire. Infection with the protozoan parasite Trypanosoma cruzi induces a hormonal systemic deregulation that has impact in the thymic S1P homeostasis that ultimately promotes the premature exit of immature CD4(-)CD8(-) T cells expressing TCR and proinflamatory cytokines to peripheral lymphoid organs, where they may interfere with adaptive immune responses. In what follows, we review recent findings revealing escape of these immature T cells exhibiting an activation profile to peripheral compartments of the immune system in both experimental murine and human models of Chagas disease.
Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.
Ana
A
Flávia Nardy
Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.
Leonardo
L
Santos
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.
Célio Geraldo
CG
Freire-de-Lima
Instituto de Microbiologia, Universidade Federal do Rio de Janeiro, 21941-590 Rio de Janeiro, RJ, Brazil.
Alexandre
A
Morrot
D000818:Animals; D014355:Chagas Disease / Q000276:immunology* / Q000473:pathology; D006801:Humans; D057131:Immune Evasion; D008246:Lysophospholipids / Q000276:immunology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000276:immunology; D060168:Thymocytes / Q000378:metabolism* / Q000473:pathology; D013950:Thymus Gland / Q000276:immunology* / Q000473:pathology; D014349:Trypanosoma cruzi / Q000276:immunology*
D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine