sTLR9 on maternal Circulating immune cells as a negative regulatory phenotype during pregnancy

TLR9 is an intracellular receptor that can also be localized to the cell surface, called sTLR9. sTLR9 is thought to have a negative immunomodulatory effect, which is conductive to the maintenance of immune tolerance. Since pregnancy is a physiological process accompanied with inflammation experienced by pregnant women while maintaining immune tolerance to the fetus, the change in sTLR9 of immune cells during pregnancy are worth studying. In this study, we first found that with the progress of pregnancy, the most significant change in PWBCs of pregnant women was the increasing percentage of neutrophils (Neu%) accompanied by the decreasing sTLR9⁺ Neu%. Then, we found that percentages and sTLR9 levels of sTLR9⁺ Neu were significantly higher in pregnant mice than those in non-pregnant mice, while the latter was obviously elevated in the first and second trimesters than that in third trimester and after delivery. In mice, the TLR9 agonist CpG ODN induced a proinflammatory environment characterized by a significant increase in Neu% and a decrease or no change in sTLR9⁺ Neu%. In this case, the delivery time of pregnant mice was not affected, but their newborn mice showed significant weight loss. These results link sTLR9 as an immune cell phenotype to immune tolerance status during pregnancy, providing a kind of new insights into the mechanisms by which pregnant mother maintain immune tolerance to the fetus.