The Unique Microbiome and Innate Immunity During Pregnancy

Abstract

A successful pregnancy depends on not only the tolerance of the fetal immune system by the mother but also resistance against the threat of hazardous microorganisms. Infection with pathogenic microorganisms during pregnancy may lead to premature delivery, miscarriage, growth restriction, neonatal morbidity, and other adverse outcomes. Moreover, the host also has an intact immune system to avoid these adverse outcomes. It is important to note the presence of normal bacteria in the maternal reproductive tract and the principal role of the maternal-placental-fetal interaction in antimicrobial immunity. Previous studies mainly focused on maternal infection during pregnancy. However, this review summarizes the new views on the study of the maternal microbiome and expounds the innate immune defense mechanism of the maternal vagina and decidua as well as how cytotrophoblasts and syncytiotrophoblasts recognize and kill bacteria in the placenta. Fetal immune systems, thought to be weak, also exhibit an immune defense function that is indispensable for maintaining the safety of the fetus. The skin, lungs, and intestines of the fetus during pregnancy constitute the main immune barriers. These findings will provide a new understanding of the effects of normal microbial flora and how the host resists harmful microbes during pregnancy. We believe that it may also contribute to the reference on the clinical prevention and treatment of gestational infection to avoid adverse pregnancy outcomes.

Keywords: NK cells; defense; innate immunity; maternal-fetus interface; microorganisms; placenta; pregnancy.

Figure 1

The antimicrobial mechanism of the vagina during pregnancy. The mechanism mainly consists of the following three parts: (1) The first barriers: tight junctions of epithelial cells, movement of microvilli, and the package of mucus, as well as natural antimicrobial peptides from epithelial cells; (2) Exclusive effect of Lactobacillus on other pernicious biota: lactic acid, acidolin, lactacin, H₂O₂; (3) The pathway including innate immune cells in the vagina, innate immune response, and acquired immune response. To be exact, antigen-derived cells, which make a sense by innate immunity, present pathogen antigens to acquired immune cells to kill, and crack pathogens.

Figure 2

Unique way of maternal-fetal interface resistance to microorganisms. (1) The main immune response in the maternal decidua: interferon (IFN)-γ secreted by natural killer (NK) cells, the most affluent cells in maternal decidua, recruits other immune cells to perform active function. Second, various antimicrobial peptides secreted by decidua cells can resist pathogenic microorganisms; (2) The cytotrophoblast relies on its diverse Toll-like receptors (TLRs) to recognize bacteria, fungi, and so on, then causes the secretion of diversity anti-inflammatory factors that activate specific immune cells; (3) The defensive role of syncytiotrophoblast is mainly from the hardness of its cells consisting of branching microvilli and complex actin network as well as maternal macrophages.