Placentation-related effects on decidual macrophages

In this study we will investigate the function of specific immune cells during pregnancy. The immune system has many different types of cells, all playing characteristic roles in fighting infections. In recent years it became obvious that immune cells also support human pregnancy. When specific white blood cells referred to as monocytes enter different tissues in our body they change their functionality and are, from then on, defined as macrophages. Our preliminary data suggest that macrophages are the most prominent cells at the so-called maternal fetal interface during pregnancy. In this specific region two genetically distinct tissues, the fetus-derived placenta and the mothers uterus (also called decidua), come in direct contact. A healthy and uncomplicated pregnancy depends on the earliest steps during placentation when trophoblastic cells (the building block of the placenta) invade the uterus of the pregnant women allowing oxygen and nutrients to flow easily between the mother and the developing fetus. My proposed research aims to understand the interaction between these invasive trophoblastic cells and maternal macrophages, which colonize the pregnant uterus. Every year, about 30.000 babies are born with infections of a virus called human cytomegalovirus (CMV). This virus can cause severe problems in the newborn including hearing loss or developmental disabilities in approximately one in ten infected infants. We know that CMV infects and persists in macrophages, but we do not know whether macrophages that colonize the pregnant uterus are also affected. This project will close this gap by characterizing CMV infections in macrophages during pregnancy. Overall, my proposed research will hopefully help to better understand the function and diversity of macrophages during pregnancy as well as identify novel potential therapeutics for the treatment of CMV infections.

During pregnancy, the placenta is in constant dialogue with the maternal immune system. In this FWF-funded project, we investigated how this dialogue is organized at the so-called feto-maternal interface, the implantation site of the placenta (decidua basalis), and how this interaction enables a healthy pregnancy. In our work, we analysed how extravillous trophoblasts, which are specialized placental cells that invade the uterine lining (medically: decidua), influence maternal immune cells (phagocytes, known as macrophages). We were able to show that a distinct macrophage population accumulates at the feto-maternal interface, and that these cells are re-programmed by extravillous trophoblasts into pregnancy-supporting cells. These macrophages proliferate locally, secrete anti-inflammatory and tissue-remodelling factors, and promote the generation of regulatory T cells that protect the fetus (the unborn child) from rejection. In areas not affected by the placenta (decidua parietalis), macrophages behave more like classical immune cells that efficiently take up foreign material and activate T cells. In complementary work, we established a method to isolate so-called interstitial fluids from early pregnancy tissues. In these fluids, proteins originating from trophoblasts and released into the tissue or blood can be specifically detected. These proteins may serve as markers for pregnancy complications such as preeclampsia and help us understand how the placenta actively reprograms its local environment. Overall, in this project we were able to show how the placenta actively controls re-programs maternal immune cells and thereby ensures tolerance towards the fetus. We gratefully acknowledge funding by the FWF, and thus ultimately the support of all taxpayers in Austria.