By Claire O’Connell
When a baby arrives too early, it can cause problems and in some cases it can unfortunately be fatal. Why do some pregnancies end in premature birth? New research in Ireland suggests there could be a process where the mother’s immune system senses DNA from the baby in the mother’s bloodstream.
Pregnancy typically lasts around 38 to 40 weeks in humans (or even a little longer in some cases) and during this time the baby develops and grows in the womb.
But if the pregnancy ends before 37 weeks, the birth is considered pre-term. And pre-term birth is one of the leading causes of infant mortality, according to the authors of a recent paper in the Journal of Immunology.
They set out to look at how the immune system might be involved in triggering preterm birth, and what they suggest is that it could involve the immune system picking up on DNA from the baby in the mother’s bloodstream.
Previous work had shown that in pregnancies which ended in pre-term birth or involved a potentially life-threatening condition called pre-eclampsia, the mother tends to have high levels of DNA from the foetus circulating in her own blood.
This foetal DNA is in a particular state called ‘hypomethylation’, which is important because DNA from microbes is also hypomethylated. And one of the ways in which the body senses microbial DNA is through a molecule called Toll-like receptor (TLR) 9.
Toll-like receptors have become one of the hot areas in immune-system research because they are like buttons that activate segments of the immune system. And when TLR-9 detects hypomethylated DNA from a microbial source in the blood, it switches on an immune response.
Could TLR-9 also sense foetal DNA in the blood and be involved in triggering preterm birth? The experiments, by researchers at Trinity College Dublin and the Coombe Women & Infants University Hospital in Dublin point in that direction.
Their research found that human immune cells growing in the lab could be activated by mouse foetal DNA. And in mice, introducing foetal DNA into the blood was linked with pregnancy complications and foetal loss.
But where does TLR-9 come in? It turned out that if the mice were engineered so that their TLR-9 didn’t work, the foetal DNA had no obvious ill effect on the pregnancy.
That’s all very well, but we can’t engineer humans to not make TLR-9. So it’s encouraging that the scientists also saw similar effects when they blocked the actions of TLR-9 with a drug called chloroquine.
“Our work identifies a process in the mother’s immune system which can trigger pre-term birth,” says researcher Prof Luke O’Neill, director of the Trinity Biomedical Sciences Institute. “If this process can be targeted therapeutically, we might be able to stop women going into labour early, which could save the baby.”
TLR9 Provokes Inflammation in Response to Fetal DNA: Mechanism for Fetal
Loss in Preterm Birth and Preeclampsia.
Scharfe-Nugent A, Corr SC, Carpenter SB, Keogh L, Doyle B, Martin C, Fitzgerald KA, Daly S, O’Leary JJ, O’Neill LA. J Immunol. 2012 Jun 1;188(11):5706-12.