title: Altered expression of galectin-3 induces cortical thymocyte depletion and premature exit of immature thymocytes during Trypanosoma cruzi infection.
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.
authors.affiliation: Department of Pathology, Laboratory of Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
authors.forename: Elizangela
authors.initials: E
authors.lastname: Silva-Monteiro
authors.forename: Luciana
authors.initials: L
authors.lastname: Reis Lorenzato
authors.forename: Oscar
authors.initials: O
authors.lastname: Kenji Nihei
authors.forename: Mara
authors.initials: M
authors.lastname: Junqueira
authors.forename: Gabriel Adrián
authors.initials: GA
authors.lastname: Rabinovich
authors.forename: Daniel Kaiyuan
authors.initials: DK
authors.lastname: Hsu
authors.forename: Fu-Tong
authors.initials: FT
authors.lastname: Liu
authors.forename: Wilson
authors.initials: W
authors.lastname: Savino
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.forename: Déa Maria Serra
authors.initials: DM
authors.lastname: Villa-Verde
mesh_terms: D000818:Animals; D001284:Atrophy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015704:CD4 Antigens / Q000378:metabolism*; D016827:CD8 Antigens / Q000378:metabolism*; D016923:Cell Death / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D014355:Chagas Disease / Q000235:genetics / Q000378:metabolism*; D037502:Galectin 3 / Q000172:deficiency / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D013950:Thymus Gland / Q000378:metabolism* / Q000469:parasitology / Q000473:pathology; D014349:Trypanosoma cruzi
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D037502:Galectin 3; C485095:Lgals3 protein, mouse