Bi-Directional Communication Between Monocytes and Trophoblasts: in vitro Modeling and Literature Synthesis

 Successful reproduction requires a complex and dynamic relationship between maternal immune cells and the placenta, to provide both immune protection for the mother and immunotolerance to the fetus. This immune adaptation is accomplished via significant intercellular communication between monocytes and trophoblasts (placental cells) at the maternal-fetal interface. We performed a scoping review of literature to describe the current research efforts investigating the bi-directional signaling between monocytes and trophoblasts, and highlighted research documenting monocyte recruitment and phenotypic changes in the intervillous space, monocyte adhesion to the syncytiotrophoblast, and monocyte interaction with syncytiotrophoblast-derived EVs. We then outlined the creation of an in vitro model to assess monocyte-trophoblast communication and demonstrated that trophoblasts under hypoxic-like conditions (elevated HIF-1α signaling) influence monocyte expression of polarization genes as well as alter monocyte functional behaviors such as adhesion, phagocytosis, and migration. We then performed preliminary work in manipulating the THP-1 cell line to mimic the altered phenotype observed in preeclampsia, in the hope that future work will assess the impact of monocyte phenotype on interactions with the trophoblast. Our remaining work focuses on preliminary investigations into the extracellular vesicle (EV) crosstalk existing between maternal and fetal cells, as well as insights into monocyte recruitment to trophoblast signals. In total, this work aims to advance the understanding of the dynamic relationship between circulating maternal monocytes and the placenta as well as to identify how maternal disease dysregulates this relationship.