Mother’s Own Immune System May Cause Pregnancy Complications
Redirecting an expectant mother’s immune cells to prevent them from attacking the fetus might reduce complications such as stillbirth and prematurity, according to a study that identifies a cell traffic pathway that plays a critical role in the process.
The causes of premature birth and many other pregnancy complications are not completely known, but maternal infection is an important contributor, says senior author Sing Sing Way, MD, PhD, Division of Infectious Diseases. When infection strikes, maternal immune cells can “overreact” and attack the placenta as if it were a foreign invader.
Way’s study, published March 9, 2015 in The Journal of Clinical Investigation, identifies a pathway that could reduce these harmful overreactions.
“It might seem counterintuitive to prevent maternal immune cells from optimally penetrating into tissues,” says Way. “But restricting harmful immune cells’ access to developmentally delicate placental tissue represents a highly innovative therapeutic strategy.”
The research team, led by Way and first author Vandana Chaturvedi, PhD, infected pregnant mice with Listeria monocytogenes, a bacterium commonly found in food supplies that causes invasive infection in pregnant women. It is often fatal to the fetus. Mice and human share this susceptibility.
The researchers found that specialized subsets of first-responder immune cells - neutrophils and macrophages - rapidly infiltrate the placenta, producing high levels of a chemoattractant protein, CXCL9, which attracts harmful maternal T cells to attack genetically foreign placental-fetal tissue.
The finding is significant because placental cells are not programmed to express chemoattractant proteins like CXCL9. The team found neutralizing CXCL9 activity by blocking its receptor on T-cells efficiently protects against fetal injury after prenatal Listeria infections.
