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

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 infectionFil: Silva Monteiro, Elizangela. Instituto Oswaldo Cruz; BrasilFil: Reis Lorenzato, Luciana. Instituto Oswaldo Cruz; BrasilFil: Kenji Nihei, Oscar. Instituto Oswaldo Cruz; BrasilFil: Junqueira, Mara. Universidade de Sao Paulo; BrasilFil: Rabinovich, Gabriel Adrián. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Kaiyuan Hsu, Daniel. University of California; Estados UnidosFil: Liu, Fu Tong. University of California; Estados UnidosFil: Savino, Wilson. Instituto Oswaldo Cruz; BrasilFil: Chammas, Roger. Universidade de Sao Paulo; BrasilFil: Serra Villaverde, Dea Maria. Instituto Oswaldo Cruz; Brasi