Associação entre apresentação de antígeno, imunorregulação e morbidade na doença de Chagas

Abstract

It has been demonstrated that cells from innate immune response secreted prostaglandins that act as regulators of the immune response against some infectious agents as the pathogen of Chagas disease, the Trypanosoma cruzi. In this work we evaluated the onocytes/macrophages activity as regulatory cells, by the production of PGE2 and cytokines, and as antigen presenting cells (APC) in non infected individuals (NI) and patients with the indeterminate(IND) or cardiac (CARD) clinical forms of Chagas disease. We isolated peripheral blood mononuclear cells (total and not adherent) and performed cellular proliferative assays in the presence or not of T. cruzi antigens. After eighteen hours of culture, the supernatants were assayed for the presence of PGE2, IL-2, IL-4, IL-10 and IFN-g. Expression of CD14, CD19, HLA-DR, CD80 and CD86 markers were performed in the culture cells. Our data showed a high proliferative response of IND and CARD patients when compared to the NI group, in the presence of antigen. After removal of the adherentcells we observed an increase in the proliferative response of cells from the NI group. In the presence of Indomethacin, a PGE2 blocker, we observed that the proliferative response of cells from IND patients could be subdivided into high (AR) and down (BR) responders. These results demonstrate that the PGE2 inhibition influences the cellularproliferate response of IND patients. It interesting to note, that IND and CARDpatients presented similar levels of PGE2 in comparison to NI group. These data evidence that PGE2 has an important role as an immune regulatory molecule. Our results also showed higher levels of IL-2, IL-4, IL-10 e IFN-g cytokines in antigen stimulated cultures when comparied to non the stimulated. Phenotypical analyses of PBMC and NA populations demonstrated that CD14+ cells have similar expression of HLA-DR, CD80 and CD86 in cultures stimulated or not with T. cruzi antigen. IND patients cells presented lower HLA-DR and CD80 expression although not significant. Analyses of CD19+ cells in NA stimulated cultures showed higher expression of HLA-DR and CD80 molecules when compared with non stimulated cultures. These results demonstrated that in the absence of macrophages, B-lymphocytes may function as antigen presenting cells. These data suggest that in presence of T. cruzi, APC function of B-lymphocytes is regulated by macrophages, independent of the secondary response, since NI cells presented the same phenotypical profile by the patients with Chagas disease.