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

Congenital transmission of <i>Trypanosoma cruzi</i> 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 <i>T. cruzi</i> (TcI) and human trophoblastic cells during <i>in vitro</i> 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 <i>T. cruzi</i> infection.<b>IMPORTANCE</b>Congenital transmission of <i>Trypanosoma cruzi</i>, the causative agent of Chagas disease, remains a significant global health concern. However, the mechanisms by which the parasite crosses the placenta and impacts fetal development are not yet fully understood. This study investigates the interaction between <i>T. cruzi</i> and trophoblastic cells-key components of the placental barrier-by analyzing transcriptomic changes in both the parasite and the host during infection. The findings provide insight into the molecular alterations associated with congenital infection and contribute to a better understanding of the host-parasite dynamics at the maternal-fetal interface. These results offer a valuable resource for advancing research into the biological processes underlying congenital Chagas disease.