Altered expression of galectin-3 induces cortical thymocyte depletion and premature exit of immature thymocytes during Trypanosoma cruzi infection

Elizangela Silva-Monteiro, Luciana Reis Lorenzato, Oscar Kenji Nihei, Mara Junqueira, Gabriel Adrián Rabinovich, Daniel Kaiyuan Hsu, Fu-Tong Liu, Wilson Savino, Roger Chammas, Déa Maria Serra Villa-Verde

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Abstract

During acute infection with Trypanosoma cruzi, the causative agent of Chagas' disease, the thymus undergoes intense atrophy followed by a premature escape of CD4+CD8+ immature cortical thymocytes. Here we report a pivotal role for the endogenous lectin galectin-3 in accelerating death of thymocytes and migration of these cells away from the thymus after T. cruzi infection. We observed a pronounced increase in galectin-3 expression that paralleled the extensive depletion of CD4+CD8+ immature thymocytes after infection. In vitro, recombinant galectin-3 induced increased levels of death in cortical immature thymocytes. Consistent with the role of galectin-3 in promoting cell death, thymuses from gal-3-/- mice did not show cortical thymocyte depletion after parasite infection in vivo. In addition, galectin-3 accelerated laminin-driven CD4+CD8+ thymocyte migration in vitro and in vivo induced exportation of CD4 +CD8+ cells from the thymus to the peripheral compartment. Our findings provide evidence of a novel role for galectin-3 in the regulation of thymus physiology and identify a potential mechanism based on protein-glycan interactions in thymic atrophy associated with acute T. cruzi infection.

Original languageEnglish (US)
Pages (from-to)546-556
Number of pages11
JournalAmerican Journal of Pathology
Volume170
Issue number2
DOIs
StatePublished - Feb 2007

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Silva-Monteiro, E., Lorenzato, L. R., Nihei, O. K., Junqueira, M., Rabinovich, G. A., Hsu, D. K., Liu, F-T., Savino, W., Chammas, R., & Villa-Verde, D. M. S. (2007). Altered expression of galectin-3 induces cortical thymocyte depletion and premature exit of immature thymocytes during Trypanosoma cruzi infection. American Journal of Pathology, 170(2), 546-556. https://doi.org/10.2353/ajpath.2007.060389