Benznidazole treatment following acute Trypanosoma cruzi infection triggers CD8+ T-cell expansion and promotes resistance to reinfection.
Many studies have shed light on the mechanisms underlying both immunoprotection and immune dysregulation arising after Trypanosoma cruzi infection. However, little is known about the impact of benznidazole (N-benzyl-2-nitroimidazole acetamide), the drug available for clinical treatment of the infection, on the immune system in the infected host. In the present study we investigated the effect of benznidazole therapy on the lymphoid compartment during the course of experimental T. cruzi infection. Although amelioration of a variety of clinical and parasitological signs was observed in treated mice, amelioration of splenocyte expansion was not detected. Interestingly, this sustained splenomegaly observed in benznidazole-treated mice showed a preferential expansion of CD8(+) T lymphocytes. Moreover, although benznidazole treatment blocked the expansion of recently activated CD4(+) and CD8(+) T cells seen in infected hosts, benznidazole treatment led to a selective expansion of effector and memory CD8(+) T lymphocytes in association with a lower rate of apoptosis. In addition, the surviving treated animals were protected from reinfection. Together, these data suggest that, in addition to its well-known direct role in blocking parasite replication in vivo, benznidazole appears to directly affect immune regulation in T. cruzi-infected hosts.
Olivieri
Bianca Perdigão
BP
Laboratory of Cell Biology, Department of Ultrastructure and Cell Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Cotta-De-Almeida
Vinícius
V
Araújo-Jorge
Tania
T
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014355:Chagas Disease / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D009593:Nitroimidazoles / Q000627:therapeutic use*; D055502:Secondary Prevention; D013154:Spleen / Q000276:immunology; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000187:drug effects
D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole