Trypanosoma cruzi isolates naturally adapted to congenital transmission display a unique strategy of transplacental passage

Summary Chagas disease is mainly transmitted by vertical transmission (VT) in non-endemic areas and in endemic areas where vector control programs have been successful. For the present study, we isolated natural strains vertically transmitted through three generations and proceeded to study their molecular mechanism of VT. No parasitemia was detected in immunocompetent mice, but they were able to induce an immune response and colonize different organs. VT experiments revealed that infection with the different strains did not affect mating, pregnancy or resorptions, but despiting low parasitemia, VT strains reached the placenta and resulted in higher vertical transmission rates than strains of either moderate or high virulence. While the virulent strain modulated more than 2500 placental genes, VT strains modulated 150, and none of the modulated genes is shared between them. VT strains downregulate genes associated with cell division and replication and upregulate immunomodulatory genes leading to anti-inflammatory responses and tolerance. The virulent strain stimulates a strong pro-inflammatory immune response, and this molecular footprint correlated with histopathological analyses. We herein describe a unique placental response regarding the passage of T cruzi VT isolates across the maternal-fetal interphase, challenging the current knowledge derived mainly from studies of laboratory-adapted or highly virulent strains.