Infecção placentária por Trypanosoma cruzi: papel da proteína P21 e avaliação do potencial terapêutico da óleo-resina e extrato hidroalcoólico das folhas de Copaifera multijuga

Abstract

Congenital Chagas disease (CCD), caused by the transplacental transmission of Trypanosoma cruzi, can lead to severe fetal complications. However, the mechanisms of placental barrier transposition and the parasite molecules involved remain poorly understood. Among these molecules, the P21 protein stands out for mediating cellular invasion and proliferation, in addition to exhibiting diverse biological activities. Given the limitations of conventional treatment with benznidazole and nifurtimox, compounds from the Copaifera genus emerge as promising therapeutic alternatives. This study aimed to fulfill two general objectives: (I) to evaluate the effects of the oleoresin (OR) and the leaf hydroalcoholic extract (LHE) of Copaifera multijuga on T. cruzi infection in trophoblastic cells (BeWo) and third-trimester human placental explants; and (II) to investigate the role of P21 in this infection using BeWo cells and both first- and third-trimester placental explants. Regarding the first objective, both compounds reduced invasion, proliferation, and trypomastigote release in BeWo cells and placental explants, altering parasite morphology and modulating the immune response (cytokines and reactive oxygen species). This demonstrates the potential of C. multijuga in controlling infection at the maternal-fetal interface. Regarding the second objective, the absence of P21 (p21-/-) reduced the parasite's invasive capacity in BeWo cells, although it increased its initial proliferation. In placental explants, however, the lack of P21 impaired T. cruzi proliferation, retaining it within the syncytiotrophoblast and altering the local inflammatory profile (particularly in the first trimester), without preventing the infection-induced collagen reduction in the third trimester. In conclusion, the P21 protein is essential for the establishment and modulation of T. cruzi infection at the maternal-fetal interface.