ABSTRACT
Several alterations involving peripheral lymphoid organs have been extensively described after experimental Trypanosoma cruzi infection. Thymic involution occurs as well in infected mice, with both structural and functional alterations in the organ. Despite these abnormalities, specific immune response proceeds to control parasitemia and the participation of T lymphocytes is essential. However, there are relatively few studies on the impact of benznidazole (N-benzyl-2-nitroimidazole acetamide) upon this response. In this present work, we decided to evaluate the impact of benznidazole treatment upon the thymus involution following acute T. cruzi infection in mice. We have provided evidence that benznidazole treatment controls the severe abnormalities seen in the thymus due to T. cruzi infection. The thymocyte loss related to the depletion of double-positive CD4(+)CD8(+) thymocytes was clearly prevented, corroborating the idea that the mechanism responsible for the prevention of thymus involution is related to the decrease of apoptosis rate in this subset after benznidazole treatment. Furthermore, we demonstrated the prevention of enhanced extracellular matrix deposition in the thymus. In conclusion, the preservation of thymus homeostasis, even though partial, was accomplished after benznidazole treatment. Our data are consistent with the notion that different outcomes of T. cruzi infection may be linked to differences in the parasite load concomitant to fine tuning of the host immune response.
Subject(s)
Apoptosis/drug effects , CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/drug effects , Chagas Disease/drug therapy , Chagas Disease/pathology , Nitroimidazoles/therapeutic use , Thymus Gland/pathology , Trypanocidal Agents/therapeutic use , Trypanosoma cruzi , Animals , Atrophy , CD4 Lymphocyte Count , Cell Death/drug effects , Chagas Disease/parasitology , Flow Cytometry , Fluorescent Antibody Technique , Male , Mice , Microscopy, Confocal , PhenotypeABSTRACT
It is well demonstrated that the thymus gland is under neuroendocrine control. Thymic endocrine function can be modulated by a variety of hormones including those secreted by the thyroid gland. This prompted us to investigate putative influences of T3 in further aspects of thymus physiology. We showed that T3-treated animals exhibited an increase in thymus weight, cellularity and cycling cells. Moreover, Thy1+ thymocytes as well as CD4-CD8 defined subsets were augmented in absolute numbers, whereas PgP.1+ cells increased in both absolute and percentage values. In parallel, the total numbers of thymic nurse cells were also increased. Regarding the expression of extracellular matrix components (ECM) by microenvironmental cells, we observed an enhancement in the intrathymic ECM upon T3 in vivo treatment. Similar effects were found in vitro by treating a thymic epithelial cell line or thymic nurse cell-derived epithelial cultures with T3. This treatment also increased the expression of ECM receptors by thymic epithelial cultures. Interestingly, an enhancement in thymocyte/thymic epithelial cell adhesion ratio was observed after T3 treatment of epithelial cells. Our data suggest that T3 exerts a pleiotropic effect upon thymus physiology, stimulating thymocyte differentiation, not only by modulating epithelial cell hormonal secretion but also their production of ECM proteins and respective receptors.
