During pregnancy, the maternal immune system must engage in a fine balancing act: maintaining tolerance to the fetal allograft while restoring innate and adaptive immune mechanisms for protection against microbial challenges. The pregnant uterus is characterized by high number of natural killer (NK) cells and macrophages and low number of dendritic cells and regulatory T cells (Treg). The interaction between immune cells, decidual stromal cells, and trophoblasts constitute a vast network of cellular connections at the maternal-fetal interface. The achievement of successful implantation, placental development, and fetal growth, as well as the maintenance of maternal and fetal health, hinges on the delicate balance of the immune response. The excessive activation of the immune system amplifies the risk of fetal rejection and adverse pregnancy outcomes such as spontaneous abortion and early pregnancy loss, preterm labor, preterm birth, fetal growth restriction, gestational diabetes and gestational hypertension including preeclampsia and HELLP syndrome.

The feto-maternal interface is still considered an enigmatic district from the immunological point of view, due to the complex biological mechanisms that have not yet been fully elucidated, such as the capability to create a tolerant environment towards the nonself-embryonic antigens but acting simultaneously as a barrier capable of defending the fetus from the attack of pathogens as decidua may be a primary site of replication for several TORCH pathogens and could thus form a reservoir for pathogens at the key site of the maternal–fetal interface. Immune system disturbances can precipitate maternal or fetal infection. The close interconnection and cross-talk between innate and adaptive immunity means that appropriate regulation of both immune systems is necessary during pregnancy. Relevant studies elucidating the complexity of interactions at the feto-maternal interface and how these interactions are modulated by pathogens are crucial in developing targeted therapeutics.

Currently, the study of the immune system at the uterine and placental levels is assuming greater interest for several reasons such as the increased use of medically assisted procreation techniques, in particular, those involving oocyte donation; the augmentation of the incidence of pregnancy pathologies connected to the older maternal age; the high number of recurrent spontaneous abortion especially related to recurrent implantation failure after In Vitro Fertilization (IVF).

This special issue aims to shed light on these unclear mechanisms that are crucial for the development of novel diagnostic tools and innovative therapeutic approaches. The articles on this topic will include original research and comprehensive reviews and will fall into 3 general categories:

1. The importance of innate immune cells, role of the complement system and an evaluation of innate immunity in infections in pregnancy and in adverse pregnancy outcomes.

2. Adaptive response in orchestrating a normal pregnancy or contributing to pathophysiology of adverse pregnancy outcomes.

3. Autoantibodies and autoimmunity in implantation and pregnancy

The topic editors declare no conflicts of interest in relation to the editorship of this collection.

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