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 infection.
Silva-Monteiro
Elizangela
E
Department of Pathology, Laboratory of Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Reis Lorenzato
Luciana
L
Kenji Nihei
Oscar
O
Junqueira
Mara
M
Rabinovich
Gabriel Adrián
GA
Hsu
Daniel Kaiyuan
DK
Liu
Fu-Tong
FT
Savino
Wilson
W
Chammas
Roger
R
Villa-Verde
Déa Maria Serra
DM
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
D015704:CD4 Antigens; D016827:CD8 Antigens; D037502:Galectin 3; C485095:Lgals3 protein, mouse