Maternal microbial exposure provides novel insights into the balance between tolerance and host defense during pregnancy 2984

Abstract Description A healthy pregnancy is an immunological phenomenon. While tolerance to fetal antigens is essential to fetal survival, the maternal immune system must simultaneously protect the fetus from pathogens. CD4 T cells are known to play an important role in maintaining this balance at the maternal fetal interface (MFI). In humans, T cells accumulate over gestation to become the most prominent immune cell type by the third trimester; however, specific pathogen free (SPF) mice have very few T cells at the MFI. We used a pet store co-housing mouse model to investigate the effect of natural microbial exposure (NME) on MFI immune cells. We found T cells were dramatically expanded at the MFI of NME dams and phenocopied the human T cell landscape. The NME model represents a significant step forward in modeling reproductive immunology. We used flow cytometry to analyze CD4 T cells from the MFI of SPF and NME dams at 14.5 days gestation. NME mice had an increase in both Th17 and Tregs compared to SPF mice, but Th1 levels remained similar. Tregs likely increased to maintain tolerance, while Th17 cells likely increased to combat the increase in extracellular pathogens. We also observed an increase in IL-23R expressing gd T cells in the MFI of NME dams, which have been shown to regulate Th17 and Th1 activation by taking up the available IL23. Overall, the NME model better represents the dynamics of the immune composition at the MFI to ensure balance between protection and tolerance mechanisms. Topic Categories Mucosal and Regional Immunology (MUC)