Placental Microenvironment Reprograms Innate Immune Cells to Prevent Inflammation

In addition to their established role in fighting pathogens, certain maternal immune cells (neutrophils) can support early placental development by supporting placental cells migrate into the uterine lining.

A MedUni Vienna research team has shown that the placental environment can reprogram these immune cells so that they support important developmental processes instead of triggering harmful inflammatory responses. The findings were published in the journal Science Immunology.

Neutrophils are part of the immune system's first line of defense and are best known for fighting pathogens. In early pregnancy, however, some of these cells appear to take on a different role, as shown by the team led by Jürgen Pollheimer at the Department of Obstetrics and Gynecology of the Medical University of Vienna.

Early in pregnancy, specialized placental cells migrate into the uterine lining. There they anchor the placenta in maternal tissue and help remodel the mother's blood vessels. These processes ensure an adequate blood supply to the embryo and are essential for a successful pregnancy. At this interface, the researchers found particularly large numbers of neutrophils. These cells differ markedly from neutrophils circulating in the blood. In laboratory experiments, tissue neutrophils increased the motility of placental cells, supporting them migrate into maternal tissue.

Reprogrammed Immune Cells Support the Placenta

Neutrophils from the same patients' blood initially damaged placental cells. The researchers showed that signals from the placental environment can change this behavior. Once reprogrammed, blood-derived neutrophils no longer caused damage and instead supported placental cell movement. Tissue neutrophils released MMP-9, which enhanced placental cell motility and activated TGF-β produced by the placenta. Active TGF-β, in turn, helped reprogram blood-derived neutrophils. Together, these findings show how placental cells and maternal neutrophils influence one another.

This two-way exchange illustrates how adaptable neutrophils are. Depending on their environment, neutrophils can fight pathogens and trigger inflammatory responses or support normal developmental processes. Whether this function changes in pregnancy complications remains to be determined in further studies.

The study was led by Jürgen Pollheimer in collaboration with MedUni Vienna's Core Facilities and the group of Gernot Schabbauer at the Institute of Vascular Biology and Thrombosis Research, as well as the groups of Michael Angelo and Sean Bendall at Stanford University. Pollheimer's Maternal-Fetal Immunology Group (MFIG) is part of the Reproductive & Obstetric Research Unit of the Division of Obstetrics and Feto-Maternal Medicine at MedUni Vienna's Department of Obstetrics and Gynecology.