Placental macrophages: Their development and role in the placenta

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The placenta, the first organ the fetus makes, is the interface between the mother and baby. A normally functioning placenta is crucialfor successful pregnancy. Macrophages are key to the healthy function of all organs, adopting specific properties to meet the needs ofthe tissue where they reside. Hofbauer cells (HBC) are fetal-derived macrophages found within the placental villous tree. However,their exact characteristics and functions are quite obscure despite being the only placental immune cell. The early appearance ofthese cells at 18 days post conception and their high abundance indicates that they play an important role in placental developmentand function. As they are located at this important barrier site, we propose that HBC also protect the placenta and fetus frominfection.My recent published work has characterised HBC and their precursors. We also defined a population of placental associated maternalmacrophages (PAMM), that are derived from maternal monocytes in the intervillous space. PAMM are found adhered to sites ofdamage on the syncytium, the outer trophoblast layer. My work has provided an important framework for the study of humanplacental macrophage populations.This research proposal will establish the human placenta as a unique haematological niche (Aim 1) and will determine how HBCregulate trophoblast biology in both early and late pregnancy (Aim 2). Finally, we will establish the roles of placental macrophages intwo important global problems, maternal obesity (Aim 2) and transplacental infection, focusing on the major vertically transmittedpathogen, human cytomegalovirus (Aim 3). These research objectives will be achieved through sequencing techniques and in vitroassays developed in my lab.By increasing our understanding of HBC new insights will emerge about human placental development and how this underpinspregnancy disorders.