Contribution of macrophages to fetomaternal immunological tolerance

The semi-allogeneic fetus develops in a uniquely immune tolerant environment within the uterus. For successful pregnancy, both the innate and adaptive immune systems must favor acceptance of the fetal allograft. Macrophages are the second most abundant immune cells after natural killer (NK) cells in the decidua. In coordination with decidual NK cells and dendritic cells, macrophages aid in implantation, vascular remodeling, placental development, immune tolerance to placental cells, and maintenance of tissue homeostasis at the maternal-fetal interface. Decidual macrophages show the classical activated (M1) and alternatively activated (M2) phenotypes under the influence of the local milieu of growth factors and cytokines, and appropriate temporal regulation of the M1/M2 switch is vital for successful pregnancy. Disturbances in the mechanisms that control the M1/M2 balance and associated functions during pregnancy can trigger a spectrum of pregnancy complications ranging from preeclampsia and fetal growth restriction to preterm delivery. This review addresses various mechanisms of tolerance, focusing on the basic biology of macrophages, their plasticity and polarization, and their protective roles at the immune-privileged maternal-fetal interface, including direct and indirect roles in promoting fetomaternal immune tolerance.