ALTERED EXPRESSION OF GALECTIN-3 INDUCES CORTICALTHYMOPCYTE DEPLETION AND PREMATURE EXIT OF IMMATURE THYMOCYTES DURING T. CRUZI INFECTION

ELIZANGELA SILVA-MONTEIRO; LUCIANA REIS-LORENZATO; OSCAR KENJI-NIHEI; MARA JUNQUEIRA; GABRIEL A. RABINOVICH; DAN HSU; FU-TONG LIU; WILSON SAVINO; ROGER CHAMMAS; DEA M. SERRA VILLA-VERDE

AMERICAN JOURNAL OF PATHOLOGY

American Society for Investigative Pathology

Lugar: United States; Año: 2007 vol. 170 p. 546 - 556

0002-9440

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