A infecção murina pelo Trypanosoma cruzi clone Sylvio X10/4: envolvimento do sistema imune no controle da parasitemia [thesis]

Giovana Giacomini
A infecção murina pelo Trypanosoma cruzi clone Sylvio X10/4: envolvimento do sistema imune no controle da parasitemia São Paulo 2012 Palavras-chave: Trypanosoma cruzi. Doença de Chagas. Parasitemia. Anticorpos. IFN-. Proteínas de fase aguda. ABSTRACT GIACOMINI, G. The murine infection by Trypanosoma cruzi clone Sylvio X10/4: immune system involvement in parasitemia control. 2012. 75 p. Masters thesis (Immunology) -Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, 2012.
more » ... panosoma cruzi, the parasite responsible for Chagas´ disease, displays wide heterogeneity and includes virulent isolates and low-virulence ones which only yield patent parasitemias in immunodeficient mice. Few studies analyzed the in vivo infection with low virulence T. cruzi parasites in spite these may account for a large portion of human cases. Here we explored the involvement of the immune system in the low level parasitemia of mice infected with low-virulence Sylvio X10/4 parasites. C57BL/6 (WT) mice inoculated intravenously (i.v.) with tissue culture Sylvio X10/4 parasites do not show patent parasitemias after 24 hours and the blood clearance curves of these parasites being similar to those of tissue culture Y strain parasites (a high-virulence isolate). Meanwhile, if the inoculated trypomastigotes were isolated from immunodeficient infected mice (SCID or RAG2KO) we observed that Y parasites leave the bloodstream more slowly than Sylvio X10/4 parasites do. Analysis of parasite loads at different organs 24 hours after i.v. parasite inoculation revealed that, in spite of the known myotropism of Sylvio x10/4, most injected parasites go to the liver and spleen, as well as infection with Y strain, suggesting an active removal process. The involvement of natural antibodies in Sylvio X10/4 removal was discarded by comparing the blood clearance curves in wild-type or SCID mice (which lack antibodies). A small participation of the complement system was suggested by analyzing Sylvio X10/4 parasitemia in WT mice depleted of C3 by cobra venom factor (CVF) treatment. Our observation that Sylvio X10/4-infected IFN-KO mice showed intermittent patent parasitemias in the first weeks of infection can not be attributed to deficiency in the production of acute phase proteins, in as much as these mice were found to secrete high levels of serum amyloid A and serum amyloid P. As infection by Sylvio X10/4 parasites progressed, parasite-specific antibodies became crucial for parasite control, given that infected BKO mice succumbed to infection in 2-3 months. In addition, a protective role was suggested for parasite-specific IgM since CD28KO mice, which do not produce specific IgG, are more resistant than BKO to infection by Sylvio X10/4; moreover, the acute phase proteins do not appear to be related to immunodeficiency of these animals. Thus, we suggest that the rapid clearance that follows Sylvio X10/4 i.v. inoculation is an active removal process. At the long run, not only IgG, but also IgM parasite-specific antibodies play an important role in protection.
doi:10.11606/d.42.2013.tde-17062013-103436 fatcat:cnnsuhbezremfnxugqt2ahc3fa