Estudos da interação Trypanosoma cruzi hospedeiro mamífero enfatizando a resposta imunológica e caracterização biológica da proteína P21 do parasito

Abstract

Trypanosoma cruzi is the etiologic agent of Chagas disease. Due to its genetic diversity, species have been divided into six groups denominated Discrete Typing Units (DTU I to VI). The G strain belongs to T. cruzi I group and CL to T. cruzi VI. Extracellular amastigotes forms (EA) are considered important in maintaining the vertebrate host cycle. Studies concerning the difference of infectiveness and the characterization of immunologic susceptibility in parasites belonging to different groups are relevant so that therapies based upon immunological response may be efficient for all distinct phylogenetic groups. T. cruzi´s P21 protein has recently been characterized and its probable action in parasites internalization process into host cell was observed. To give continuity to the functional characterization of T. cruzi´s P21 employing its recombinant form (P21-His6) is of great relevance taking into account that these could in the future take part into the potential therapeutic goals. The objectives of this study were to analyze the immunological profile by T. cruzi infection, seeking to identify the differentiated performance of this response against G and CL strains and different forms of the parasite (metacyclic trypomastigotes or extracellular amastigotes); to analyze the differential tropism of CL and G strains during the acute and chronic infection; characterize the biological activity of P21 T. cruzi protein, trying to analyze its function to the parasite and performance in the host cell. We observed that extracellular amastigotes from G strain does not induce patent infection in vivo due to their high susceptibility to IFN-γ production early in infection; There were differences in tropism between the different strains, since during the kinetics infection, the CL strain was maintained preferably in the stomach, both in the acute and chronic phase and G strain remained in the stomach throughout the entire infection, but was also able to migrate into the heart tissue, particularly in chronic infection; The chemokine KC seems to play an important role in controlling the infection and may influence the course of infection, as well as the possible migration of parasites; the P21-His6 enhances phagocytosis and the remodeling of the actin cytoskeleton by binding to CXCR4 receptor and activate via PI3-k.