Pregnancy and infancy are immunological periods marked by increased risk of infection. Infection during pregnancy, particularly late in gestation, is associated with fetal loss, miscarriage, and pre-term birth. For infants under six months of age, infection is the leading cause of hospitalization and death. Successful pregnancies require the maternal and developing fetal immune systems to tolerate one another. It is thought that this requirement for tolerance contributes to the relative immunosuppression during pregnancy and infancy. The requirement for tolerance of maternal antigens ceases at birth and the need for robust immunity to pathogens becomes immediate, yet the human immune system takes many months to mature. It is unknown if immune maturation can be accelerated, or whether doing so is safe or beneficial. The constraints of human research and the use of sterile animal models limit advances in these areas, particularly regarding the influence of microbial exposure on pregnancy and immune development. Commonly-used animal models are raised in “specific pathogen free” (SPF) conditions to minimize the confounding effects of microbial exposure.
This project seeks to understand how exposure to diverse microbes influences the physiology of pregnancy and infant immune development. To this end, these researchers will contrast the immune composition and function of pregnant and infant mice in the University of Minnesota’s Dirty Mouse Facility, where laboratory strains of mice are co-housed with pet store mice to normalize microbial exposure, with that of control mice maintained in the SPF facility. Based on published observations by collaborators in non-pregnant adult mice, the researchers hypothesize that microbial exposure will heighten maternal immune responses and promote robust infant immune development. The studies will reveal the effects of microbial exposure on pregnancy and infant immune development. More generally, this line of investigation will lead to a better understanding of the immunology of pregnancy, how healthy immune systems develop, and how the pregnant and infant immune systems respond to infections and microbial products. This research will also inform the risks and benefits of modulating immunity during pregnancy and infancy, which will lead to important advancements in treatments for early life infection and to novel vaccination approaches.