The Immunology of Syncytialized Trophoblast

Multinucleate syncytialized trophoblast is found in three forms in the human placenta. In the earliest stages of pregnancy, it is seen at the invasive leading edge of the implanting embryo and has been called primitive trophoblast. In later pregnancy, it is represented by the immense, multinucleated layer covering the surface of placental villi and by the trophoblast giant cells found deep within the uterine decidua and myometrium. These syncytia interact with local and/or systemic maternal immune effector cells in a fine balance that allows for invasion and persistence of allogeneic cells in a mother who must retain immunocompetence for 40 weeks of pregnancy. Maternal immune interactions with syncytialized trophoblast require tightly regulated mechanisms that may differ depending on the location of fetal cells and their invasiveness, the nature of the surrounding immune effector cells and the gestational age of the pregnancy. Some specifically reflect the unique mechanisms involved in trophoblast cell–cell fusion (aka syncytialization). Here we will review and summarize several of the mechanisms that support healthy maternal–fetal immune interactions specifically at syncytiotrophoblast interfaces.