Macrophage exosomes induce placental inflammatory cytokines: a novel mode of maternal-placental messaging

Congratulations to Dr Beth Holder on getting this beautiful paper published and thanks to the collaborators within and outside of the department who helped to facilitate the work with all the various techniques.

Beth recently presented the work at the International Symposium for Maternal and Neonatal Immunisation and her talk was praised as an outstanding contribution, particularly by our US attendees. This work was funded through theĀ Imperial NIHR Biomedical Research Centre (BRC) and the Medical Research Council.


During pregnancy, the placenta forms the interface between mother and fetus. Highly controlled regulation of trans-placental trafficking is therefore essential for the healthy development of the growing fetus. Extracellular vesicle-mediated transfer of protein and nucleic acids from the human placenta into the maternal circulation is well documented; the possibility that this trafficking is bi-directional has not yet been explored but could affect placental function and impact on the fetus. We hypothesized that the ability of the placenta to respond to maternal inflammatory signals is mediated by the interaction of maternal immune cell exosomes with placental trophoblast. Utilising the BeWo cell line and whole placental explants, we demonstrated that the human placenta internalizes macrophage-derived exosomes in a time- and dose-dependent manner. This uptake was via clathrin-dependent endocytosis. Furthermore, macrophage exosomes induced production of proinflammatory cytokines by the placenta. Taken together, our data demonstrates that exosomes are actively transported into the human placenta and that exosomes from activated immune cells modulate placental cytokine production. This represents a novel mechanism by which immune cells can signal to the placental unit, potentially facilitating responses to maternal inflammation and infection, and thereby preventing harm to the fetus.

Jane Webb
Secretary for the Section of Paediatrics and Personal Assistant to the Head of Department, Professor Andrew Bush.

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