ABSTRACT
Developing thymocytes interact with thymic epithelial cells (TECs) through cell-cell interactions, TEC-derived secretory moieties and extracellular matrix (ECM)-mediated interactions. These physiological interactions are crucial for normal thymocyte differentiation, but can be disrupted in pathological situations. Indeed, there is severe thymic atrophy in animals acutely infected with Trypanosoma cruzi due to CD4+CD8+ thymocyte depletion secondary to caspase-mediated apoptosis, together with changes in ECM deposition and thymocyte migration. We studied an in vitro model of TEC infection by T. cruzi and found that infected TEC cultures show a reduced number of cells, which was likely associated with decreased proliferative capacity, but not with increased cell death, as demonstrated by bromodeoxyuridine and annexin-V labelling. The infected TEC cultures exhibited increased expression of fibronectin (FN), laminin (LM) and type IV collagen. Importantly, treatment with FN increased the relative number of infected cells, whereas treatment with anti-FN or anti-LM antibodies resulted in lower infection rates. Consistent with these data, we observed increased thymocyte adhesion to infected TEC cultures. Overall, these results suggest that ECM molecules, particularly FN, facilitate infection of the thymic epithelium and that the consequent enhancement of ECM expression might be associated with changes in TEC-thymocyte interactions.
Subject(s)
Chagas Disease/metabolism , Epithelial Cells/metabolism , Extracellular Matrix/metabolism , Fibronectins/metabolism , Thymocytes/metabolism , Thymus Gland/metabolism , Animals , Cell Adhesion/physiology , Cell Communication/physiology , Cell Movement/physiology , Disease Models, Animal , Epithelial Cells/parasitology , Male , Mice, Inbred BALB C , Thymocytes/parasitology , Thymus Gland/cytologyABSTRACT
Developing thymocytes interact with thymic epithelial cells (TECs) through cell-cell interactions, TEC-derived secretory moieties and extracellular matrix (ECM)-mediated interactions. These physiological interactions are crucial for normal thymocyte differentiation, but can be disrupted in pathological situations. Indeed, there is severe thymic atrophy in animals acutely infected with Trypanosoma cruzi due to CD4+CD8+ thymocyte depletion secondary to caspase-mediated apoptosis, together with changes in ECM deposition and thymocyte migration. We studied an in vitro model of TEC infection by T. cruzi and found that infected TEC cultures show a reduced number of cells, which was likely associated with decreased proliferative capacity, but not with increased cell death, as demonstrated by bromodeoxyuridine and annexin-V labelling. The infected TEC cultures exhibited increased expression of fibronectin (FN), laminin (LM) and type IV collagen. Importantly, treatment with FN increased the relative number of infected cells, whereas treatment with anti-FN or anti-LM antibodies resulted in lower infection rates. Consistent with these data, we observed increased thymocyte adhesion to infected TEC cultures. Overall, these results suggest that ECM molecules, particularly FN, facilitate infection of the thymic epithelium and that the consequent enhancement of ECM expression might be associated with changes in TEC-thymocyte interactions.
Subject(s)
Animals , Male , Chagas Disease/metabolism , Epithelial Cells/metabolism , Extracellular Matrix/metabolism , Fibronectins/metabolism , Thymocytes/metabolism , Thymus Gland/metabolism , Cell Adhesion/physiology , Cell Communication/physiology , Cell Movement/physiology , Disease Models, Animal , Epithelial Cells/parasitology , Mice, Inbred BALB C , Thymocytes/parasitology , Thymus Gland/cytologyABSTRACT
Pathophysiology of Chagas' disease is not completely defined, although innate and adaptative immune responses are crucial. In acute infection some parasite antigens can activate macrophages, and this may result in pro-inflammatory cytokine production, nitric oxide synthesis, and consequent control of parasitemia and mortality. Cell-mediated immunity in Trypanosoma cruzi infection is also modulated by cytokines, but in addition to parasite-specific responses, autoimmunity can be also triggered. Importantly, cytokines may also play a role in the cell-mediated immunity of infected subjects. Finally, leukocyte influx towards target tissues is regulated by cytokines, chemokines, and extracellular matrix components which may represent potential therapeutic targets in infected patients. Here we will discuss recent findings on the role of cytokines, chemokines and extracellular matrix components in the regulation of innate and adaptive immunity during T. cruzi infection.
