ArticlePLoS neglected tropical diseases2014
Early double-negative thymocyte export in Trypanosoma cruzi infection is restricted by sphingosine receptors and associated with human chagas disease.
Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Severe fever with thrombocytopenia syndrome virus infection induces thymic atrophy in IFNARVirulence · 2025Article
- The thymus road to a T cell: migration, selection, and atrophy.Frontiers in immunology · 2024Review
- MicroRNAs: master regulators in host-parasitic protist interactions.Open biology · 2022Review
- Thymus, undernutrition, and infection: Approaching cellular and molecular interactions.Frontiers in nutrition · 2022Review
- Enhanced Migratory Capacity of T Lymphocytes in Severe Chagasic Patients Is Correlated With VLA-4 and TNF-α Expression.Frontiers in cellular and infection microbiology · 2021Article
- IFNγ and iNOS-Mediated Alterations in the Bone Marrow and Thymus and Its Impact onFrontiers in immunology · 2021Article
- PET Study of Sphingosine-1-phosphate Receptor 1 Expression in Response toMolecular imaging · 2021Article
- Infection-Associated Thymic Atrophy.Frontiers in immunology · 2021Review
- Overexpression of Sphingosine Kinase-1 and Sphingosine-1-Phosphate Receptor-3 in SevereBioMed research international · 2020Article
- The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation.Frontiers in immunology · 2020Review
- Sphingosine-1-phosphate signaling in Leishmania donovani infection in macrophages.PLoS neglected tropical diseases · 2018Article
- Sphingosine-1-Phosphate Receptor 1 Is Involved in Non-Obese Diabetic Mouse Thymocyte Migration Disorders.International journal of molecular sciences · 2018Article
- Circulating Plasma MicroRNA-208a as Potential Biomarker of Chronic Indeterminate Phase of Chagas Disease.Frontiers in microbiology · 2018Article
- Role of Hormonal Circuitry Upon T Cell Development in Chagas Disease: Possible Implications on T Cell Dysfunctions.Frontiers in endocrinology · 2018Review
- Article
- Evasion and Immuno-Endocrine Regulation in Parasite Infection: Two Sides of the Same Coin in Chagas Disease?Frontiers in microbiology · 2016Review
- Exit Strategies: S1P Signaling and T Cell Migration.Trends in immunology · 2015Review
- Immune Evasion Strategies of Trypanosoma cruzi.Journal of immunology research · 2015Review
- Laminin-Mediated Interactions in Thymocyte Migration and Development.Frontiers in immunology · 2015Review
- Modulation of Intrathymic Sphingosine-1-Phosphate Levels Promotes Escape of Immature Thymocytes to the Periphery with a Potential Proinflammatory Role in Chagas Disease.BioMed research international · 2015Review
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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-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.
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