Avaliação da participação das ecto-nucleotidases do Trypanosoma cruzi nos processos de infecção e virulência em modelo murino

AUTOR(ES)

Marcela Auxiliadora Souza Possa

DATA DE PUBLICAÇÃO

2008

RESUMO

Chagas disease is one of the main diseases with high economical and social impacts in Latin America, with millions of people with this illness. The current drugs used to treat this disease lead to low cure, especially in the chronic phase and present high toxic non- desired side effects. Because of these there are necessity to develop new drugs and strategies for the control and treatment of Chagas disease. From this point of view biochemical pathways related with surviving capacity and virulence of Trypanosoma cruzi could represent good targets. In this work we evaluate the roles of T. cruzi ecto- nucleotidases in the infection and virulence procedures in mouse, using parasites pre- treated with the known E-NTPDase inhibitors (Suramin, Gadolinium and ARL67156). The pre-treatment with all inhibitors leaded to significantly decreases in parasitemia and mortality. This influences were dose-dependent and the betters concentrations of inhibitors were: 300m, 300m and 1mM, to GdCl 3, ARL and Suramin, respectively. The pre-treatments lead to high levels of INF-γ expression in the heart and serum production, in the earlier stages of infection. These data suggest that ecto-nucleotidase inhibitions could be responsible to increments in extra-cellular ATP concentration that could stimulate hosts inflammatory mechanisms against parasites, evidencing the participation of these ecto-enzymes in the modulation of host immune system. Our data showed that the pre-treatment no change IL-10 heart expression and serum production too. In addition, when we evaluate the inflammation intensity in animal hearts, we observed that GdCl3 was able to reduce the number of inflammatory cells, both in the 8th an 15th days of infection. Concluding, together our data suggest an effective participation of parasite E-NTPDases in the infection process and in the modulation of host immune system. We believe that the inhibition of these pathways emerge as new good targets to block T. cruzi infection and to be used in specific new chemotherapy to Chagas disease.

ASSUNTO(S)

infecção doença de chagas camundongos trypanosoma cruzi imunologia impacto social

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