Avaliação da infecção aguda e crônica por tripomastigotas de Trypanosoma cruzi (TcI e TcVI) em camundongos isogênicos BALB/c e C57BL/6

• Ano de defesa: 2016
• Autor(a) principal: Ferreira, Bianca Rodrigues Lima [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Trypanosoma cruzi
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=4239461; http://repositorio.unifesp.br/handle/11600/47993

Trypanosoma cruzi is the etiologic agent of Chagas' disease, that affects millions of people worldwide. Different strains of T. cruzi present specific genotype and phenotype characteristics, that interfere with host-pathogen interactions and thus, the parasite has been classified into six groups (TcI to TcVI). T. cruzi infection develops in acute and chronic phases featured by different characteristics with an important role of the immune system that has a dual role as both protective and pathogenic element. Mouse is a well-established experimental model of Chagas' disease because it reproduces important features of human infection and provides an experimental basis for the study of host lineages and the parasite strain. Thus, we evaluated acute and chronic infection by G (TcI) and CL (TcVI) strains of T. cruzi, which have distinct tropism and infectivity, in two inbred mice lineages (C57BL/6 and BALB/c), that display variable susceptibility degrees for different T. cruzi strains. We have analyzed parasite tropism for different tissues by confocal microscopy and qPCR, and we also evaluated host responses to infection by analyzing splenic lymphocytes and peritoneal macrophages populations, besides quantifying serum cytokines and chemokines. qPCR results showed that CL strain established the infection faster than G strain; at the same time, BALB/c response, through diverse in cytokine secretion, had been initiated earlier than in C57BL/6 mice. At the parasitaemia peak in acute phase, we observed that the infection was disseminated in all groups analyzed, either by confocal microscopy or by qPCR, with some differences concerning parasite tropism; and at this point, all the animals had responded to infection by increasing serum cytokines concentration, however BALB/c mice seemed to better regulate the immune response than C57BL/6. Indeed, at the chronic phase, C56BL/6 mice presented exacerbated cytokine and chemokine responses, and also had a decrease in regulatory T cell population. Thus our results point that, in these experimental models, the deregulation of immune response, that is typical of chronic Chagas? disease, may be due to loss of pro and anti-inflammatory cytokines control early in the acute phase of the disease.