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O TRATAMENTO COM BENZNIDAZOL PROMOVE MUDANÇAS NO COMPARTIMENTO LINFOIDE DE CAMUNDONGOS INFECTADOS PELO TRYPANOSOMA CRUZI

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O tratamento com benznidazol interrompeu não apenas a replicação parasitária, mas também originou novos mecanismos regulatórios ocasionando mudanças na resposta imune.
perdigaooliveri9.jpg Autor:
Bianca Perdigão olivieri
Columnista Experto de SIIC

Institución:
Instituto Oswaldo Cruz Fundação Oswaldo Cruz

Artículos publicados por Bianca Perdigão olivieri
Coautores
Vinícius Cotta de Almeida*  Tania Araújo Jorge** 
Doutor em Ciências. Instituto Oswaldo Cruz/FIOCRUZ*
Doutora em Ciências. Instituto Oswaldo Cruz/FIOCRUZ**
Recepción del artículo
17 de Mayo, 2005 		Aprobación
7 de Junio, 2005
Primera edición
30 de Marzo, 2006 		Segunda edición, ampliada y corregida
7 de Junio, 2021

O TRATAMENTO COM BENZNIDAZOL PROMOVE MUDANÇAS NO COMPARTIMENTO LINFOIDE DE CAMUNDONGOS INFECTADOS PELO TRYPANOSOMA CRUZI

Resumen
A doença de Chagas é considerada uma doença endêmica em muitos países da América Latina. O benznidazol (N-benzil-2-nitroimidazol acetamida) é utilizado para a terapia desta doença, e o conceito de que o sucesso da terapia envolva a participação do sistema imune foi proposto. Neste texto, será feita a revisão dos principais resultados obtidos por nosso grupo no que diz respeito ao impacto da terapia com benznidazol sobre as principais populações linfocitárias presentes em órgãos linfóides durante a infecção experimental por T. cruzi. O tratamento com benznidazol atenuou as principais alterações observadas no timo, havendo redução da atrofia tímica e da eliminação de timócitos, concomitante ao restabelecimento do fenótipo normal com maioria de células imaturas CD4+CD8+, além da prevenção de depósitos de moléculas de matriz extracelular. Estes dados sugerem a preservação do compartimento linfóide central. De forma surpreendente, detectamos aumento na massa e celularidade do baço de camundongos infectados e tratados por benznidazol, relacionado à expansão preferencial de linfócitos T CD8+ com fenótipo efetor/memória. Além disso, houve modificação na relação CD4:CD8 e redução na frequência de apoptose. Em resumo, o tratamento com benznidazol interrompeu não apenas a replicação parasitária, mas também originou novos mecanismos regulatórios ocasionando mudanças na resposta imune.

Palabras clave
Benznidazol, Trypanosoma cruzi, camundongos, órgãos linfóides, linfócitos


Artículo completo
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BENZNIDAZOLE THERAPY PROMOTES CHANGES ON THE LYMPHOID COMPARTMENT OF TRYPANOSOMA CRUZI INFECTED MICE

Abstract
Chagas’ disease is endemic in most Latin American countries. The nitroderivative benznidazole (N-benzyl-2-nitroimidazole acetamide) is the most employed trypanocidal drug for Chagas’ disease and the concept that the success of anti-parasite treatment involves the immune system has been proposed. Here we review our work evaluating the impact of benznidazole therapy upon the main lymphocyte populations present in lymphoid organs in the course of experimental T. cruzi infection. Benznidazole treatment was able to lessen the severe abnormalities seen in the thymus following T. cruzi infection: it reduced thymus involution and thymocyte loss, restored the normal immature CD4+CD8+ phenotype, and prevented extracellular matrix deposits, substantiating the concept that the central lymphoid compartment is preserved. Surprisingly, in benznidazole-treated mice we detected higher spleen mass and viable cell numbers than in non-treated mice (higher splenomegaly), related to the preferential expansion of CD8+ T lymphocytes with high frequency of effector/memory cells, and a decrease in the apoptosis rate. As a consequence, a change in the CD4:CD8 ratio occurred as well. As a result, benznidazole treatment not only interrupted parasite replication but also induced new regulatory mechanisms, originating thus a different host immune response.

Key words
Benznidazole, Trypanosoma cruzi, mice, lymphoid organs, lymphocytes

Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Infectología
Relacionadas: Bioquímica, Farmacología, Salud Pública



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