The placenta’s own immune cells, called Hofbauer cells, appear just 18 days after conception and outnumber other immune cells, yet no one knows exactly what they do. These fetal-derived macrophages live inside the placental villi, the tree-like structures that exchange nutrients and waste between mother and baby. A separate population of maternal macrophages, called PAMM cells, clings to damaged patches on the placenta’s outer surface. This project will map how both cell types develop, how Hofbauer cells guide the growth of the placental barrier, and what happens when they fail—specifically in two global problems: maternal obesity and infection with human cytomegalovirus, a leading cause of birth defects. The work is fundamental science, driven by a basic gap in knowledge: we do not understand the placenta’s own immune system. If successful, it could reveal why some pregnancies go wrong and point toward ways to detect or prevent complications long before they harm mother or baby.
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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 crucial for successful pregnancy. Macrophages are key to the healthy function of all organs, adopting specific properties to meet the needs of the 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 of these cells at 18 days post conception and their high abundance indicates that they play an important role in placental development and function. As they are located at this important barrier site, we propose that HBC also protect the placenta and fetus from infection. My recent published work has characterised HBC and their precursors. We also defined a population of placental associated maternal macrophages (PAMM), that are derived from maternal monocytes in the intervillous space. PAMM are found adhered to sites of damage on the syncytium, the outer trophoblast layer. My work has provided an important framework for the study of human placental macrophage populations. This research proposal will establish the human placenta as a unique haematological niche (Aim 1) and will determine how HBC regulate trophoblast biology in both early and late pregnancy (Aim 2). Finally, we will establish the roles of placental macrophages in two important global problems, maternal obesity (Aim 2) and transplacental infection, focusing on the major vertically transmitted pathogen, human cytomegalovirus (Aim 3). These research objectives will be achieved through sequencing techniques and in vitro assays developed in my lab. By increasing our understanding of HBC new insights will emerge about human placental development and how this underpins pregnancy disorders.
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