Dual transcriptomics suggests trophoblastic sequestration and splicing blockade induced by Trypanosoma cruzi during in vitro infection

Congenital transmission of Trypanosoma cruzi is a significant public health concern, involving complex interactions between the parasite, the placenta, and the fetus. However, the mechanisms facilitating parasite passage across the placental barrier remain incompletely understood. This study explores the transcriptional response of both T. cruzi (TcI) and human trophoblastic cells during in vitro infection, aiming to provide insights into parasite-host interactions relevant to congenital Chagas disease. Two TcI strains (MHOM/CO/01/DA and MHOM/CO/04/MG) were used to infect BeWo cells, and RNA was sequenced at 72 and 120 h post-infection. The MG strain exhibited higher invasion and replication rates than the DA strain. Transcriptomic analysis of the parasite revealed modulation of 157 genes, including several encoding surface-associated multigene families potentially involved in host interaction. In host cells, the upregulation of histones and ribonucleoproteins suggested chromatin remodeling, while the downregulation of RNA splicing-related genes pointed to alterations in RNA processing. At 120 h, genes associated with necroptosis were upregulated, indicating a shift in the host cell response. Overall, these results highlight key molecular changes during trophoblast infection by TcI strains and provide a transcriptomic resource for advancing the understanding of congenital T. cruzi infection.