In pregnancy, successful implantation, placental development, and fetal growth, as well as maintenance of both maternal and fetal health, requires immune balance. In case of excessive activation of the immune system, the risk of rejection of the fetus and adverse pregnancy outcomes such as preeclampsia or gestational hypertension may arise. In addition, deficiencies of the immune system can lead to maternal or fetal infection. Due to known cross-talk, both innate and adaptive immunity must be properly regulated. The current Research Topic, however, will focus on the innate immune system, both in its role in adverse pregnancy outcomes, as well as its essential role in normal progression of pregnancy and fetal development.

Previous studies have clearly shown that complement is essential for normal placental and fetal development, but excessive complement activation in hypoxic placenta or in autoimmune-related pregnancy complications is detrimental for both mother and child. NK cells are essential for proper trophoblast migration and placental development, but inappropriate NK cell activation may lead to symptoms of preeclampsia. TLR and inflammasome activation in neutrophils and macrophages are essential for protecting the fetus from infection, whereas excessive activation may result in chronic inflammation, hypertension, endothelial dysfunction and placental damage. Auto-reactive natural occurring antibodies from B1 cells may also be instrumental in the pathophysiology of pregnancy complications. Genetic modifications of any of these innate immune responses can influence susceptibility and immunopathology during pregnancy. In addition, obesity, hypertension, and metabolic disorders contribute as risk factors for adverse pregnancy outcomes.

This Research Topic calls for Original Research, Review, Clinical Trial, Methods, and Perspective articles focusing on, but not limited to, the following subtopics in normal and adverse pregnancy:

1. Role of innate immune cells, including macrophages, neutrophils, innate B1 cells, and NK cells
2. Role of the complement system
3. Role of TLRs
4. Role of autoreactive natural antibodies