The architecture of early-life immunity
The architecture of early-life immunity
Pregnancy is a remarkable biological balancing act. During pregnancy, a mother’s immune system must protect both herself and her unborn child from infections while at the same time tolerating the developing fetus. When this balance is disturbed, complications such as preterm birth and fetal growth restriction can occur. These complications affect millions of pregnancies worldwide and can have lifelong consequences for children.
This thesis of Sharon Eskander explores how the immune system develops and functions before birth. By studying the fetal brain, the placenta, and fetal blood, it provides new insights into the complex interactions between maternal, placental, and fetal immunity.
One focus of this work was microglia, the immune cells of the developing brain. These cells play an important role in shaping brain development. The research shows that human microglia already acquire immune-sensing properties early in pregnancy, suggesting that the prenatal environment may influence brain development much earlier than previously thought.
The thesis also investigates placental macrophages, specialized immune cells that help maintain a healthy pregnancy. A new method was developed to isolate these cells while minimizing artificial changes caused by laboratory procedures, allowing researchers to study them more accurately.
Finally, advanced multi-omics technologies were used to investigate immune changes associated with preterm birth and fetal growth restriction. The results reveal distinct immune signatures for these complications and identify potential biomarkers that may help predict adverse pregnancy outcomes in the future.
Together, these findings improve our understanding of how the immune system shapes early life and may contribute to better diagnostic tools and interventions to improve the health of both mothers and children.