Fibronectin modulates thymocyte-thymic epithelial cell interactions following Trypanosoma cruzi infection

Developing thymocytes interact with thymic epithelial cells (TECs) through cell-cellinteractions, TEC-derived secretory moieties and extracellular matrix (ECM)-mediatedinteractions. These physiological interactions are crucial for normal thymocytedifferentiation, but can be disrupted in pathological situations. Indeed, there is severethymic atrophy in animals acutely infected with Trypanosoma cruzi due toCD4+CD8+ thymocyte depletion secondary to caspase-mediated apoptosis, together withchanges in ECM deposition and thymocyte migration. We studied an in vitro model of TECinfection by T. cruzi and found that infected TEC cultures show a reducednumber of cells, which was likely associated with decreased proliferative capacity, butnot with increased cell death, as demonstrated by bromodeoxyuridine and annexin-Vlabelling. The infected TEC cultures exhibited increased expression of fibronectin (FN),laminin (LM) and type IV collagen. Importantly, treatment with FN increased the relativenumber of infected cells, whereas treatment with anti-FN or anti-LM antibodies resulted inlower infection rates. Consistent with these data, we observed increased thymocyteadhesion to infected TEC cultures. Overall, these results suggest that ECM molecules,particularly FN, facilitate infection of the thymic epithelium and that the consequentenhancement of ECM expression might be associated with changes in TEC-thymocyteinteractions.