Maternal-fetal immune interactions: Implications for intrauterine infections: A review

Abstract

In this review the problem of intrauterine infection of the fetus has been discussed in the light of knowledge gained from studying the immunology of maternal-fetal interactions. The non-classical HLA class I molecule HLA-G is expressed exclusively by extravillous trophoblast cells and has been proposed to play a role in protecting the fetus from maternal infection. However, the anatomical site of HLA-G expression, the diminishing expression of HLA-G throughout gestation, the lack of HLA-G reactive T cells and the minimal polymorphism would argue against this role. It is also difficult to ascribe a function for the endometrial and decidual natural killer (NK) cells in combating infectious diseases. These NK cells have similar characteristics to NK cells circulating in adult blood, which are known to be important in the defense against viral infections. However, since uterine NK cells are only present in large numbers in the progesterone stimulated uterine mucosa and are sparse in the proliferative phase of the normal menstrual cycle, it is difficult to envisage how these cells can be a vital component of the uterine mucosal defense. Systemic immune responses during pregnancy appear to be deviated toward Th2 away from Th1. This phenomenon will affect the severity of disease and transplacental transmission of infection caused by intracellular and extracellular pathogens. Transfer of immunoglobulins across the placenta is via a specific receptor, FcRn, which structurally resembles an HLA class I molecule. As well as transfering protective antibodies to the fetus, potentially harmful auto-antibodies may also cross. However, some alloantibodies directed to paternally encoded antigens can be removed by placental cells, giving rise to the idea of the placenta acting as an “immunological sponge”. In conclusion, it is clear that a study of the immunology of the fetal-maternal interaction could provide a new perspective on intrauterine infection.