Gut microbiota promote immune tolerance at the maternal-fetal interface 3952

Abstract Description Immune tolerance at the maternal-fetal interface is required for fetal development. Excessive maternal interferon gamma (IFNγ) and interleukin-17 (IL-17) responses is linked to adverse effects on fetal growth, but the regulation of maternal IFNγ and IL-17 response at the maternal-fetal interface is poorly understood. Here we demonstrate a gut-placenta immune axis during pregnancy in mice in which the gut microbiota promotes a tolerogenic immune landscape at the maternal-fetal interface. Germ-free or antibiotic-treated mice exhibit an imbalance in IFNγ and IL-17 responses at the maternal-fetal interface, including an elevation of fetus-specific T cells, resulting in increased fetal resorption. Microbiota-primed myeloid-derived suppressor cells and RORγt+ regulatory T cells travel to the maternal-fetal interface and control the balance of IFNγ and IL-17 responses, respectively. We further find that microbiota-derived aryl hydrocarbon receptor (AhR) ligands access the amniotic fluid and promote immune tolerance at the maternal-fetal interface; supplementation of an AhR agonist, indole-3-carbinol, or AhR ligand-producing Lactobacillus murinus, restores a balanced T cell response at the maternal-fetal interface and reduces fetal resorption in germ-free mice. Together, our findings identify novel microbiota-dependent immune tolerance mechanisms that promote fetal development. Funding Sources NIH/NICHD R01HD110118; NIH/NHLBI R01HL169989; NIH/NCI R21CA27099; NIH/NIDDK K01DK114376; NIH/NIAID R01AI123368; NIH/NIAID R01AI125264; NIH/NICHD 1F32HD112151; Hartwell Fndn; Starr Cancer Consortium; NCATS 2TL1-TR-2386; NCATS 2KL2-TR-2385; Biocodex Microbiota Fndn; NIH/NIDDK 3T32DK116970-05S1; Crohn’s and Colitis Fndn??? Topic Categories Mucosal and Regional Immunology (MUC)