Benznidazole therapy in Trypanosoma cruzi-infected mice blocks thymic involution and apoptosis of CD4+CD8+ double-positive thymocytes.
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.
Olivieri
B P
BP
Laboratory of Cell Biology, Department of Ultrastructure and Cell Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Ave. Brasil 4365, Rio de Janeiro, Brazil CEP 21040-900. olivieri@ioc.fiocruz.br
Farias-De-Oliveira
D A
DA
Araujo-Jorge
T C
TC
Cotta-de-Almeida
V
V
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001284:Atrophy; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D009593:Nitroimidazoles / Q000627:therapeutic use*; D010641:Phenotype; D013950:Thymus Gland / Q000473:pathology*; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi
D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole