Plasmodium falciparum infection of the placenta leads to global and local alterations in spatially-resolved gene expression of maternal and fetal tissue.. Spatially-resolved transcriptomics of the maternal-fetal interface in pregnancy-associated malaria.

Malaria during pregnancy can have severe consequences for both the mother and the fetus, including maternal anemia, preterm delivery, low birth weight, abnormal gestational growth, and maternal and neonatal mortality. The principal biological underpinning of pregnancy-associated malaria is the sequestration of parasites in the placenta, which can lead to major dysregulation of placental structures and functions. Our study leverages spatially-resolved gene expression analysis of placental tissue from infected and uninfected volunteers in Benin to define the alterations caused during pregnancy-associated malaria in different placental structures. We observe dysregulation of key functions in the placenta, especially linked to hypoxia, detoxification, inflammation, hormonal response, and fetal development. Moreover, we identify molecular signatures of immune cell recruitment and response in infected placentae revealing spatially-distinct immune regulation. We further leverage our data to identify sequestered parasites within tissue sections and define local dysregulation in response to the presence of the parasite. Altogether our study demonstrates the global and local consequences of parasite sequestration within placentae and provides a deeper understanding of pregnancy-associated malaria.