Immune Cells in the Placental Villi Contribute to Intra-amniotic Inflammation

Intra-amniotic inflammation is associated with preterm birth, and significant morbidities for both the mother and fetus. Prior studies have illustrated many of the effects of intra-amniotic inflammation on the uterine lining (decidua) and membranous layers of the placenta at the fetal maternal interface. However, much less is known about the immunological response occurring within the villous placenta. Using a rhesus macaque model of LPS-induced intra-amniotic inflammation, we showed that pregnancy-matched choriodecidua and villi have distinct immunological profiles in Rhesus monkeys. We demonstrate a complex and diverse immune landscape within the placental villi with alterations in B cell, monocyte and CD8 T cell abundances upon LPS treatment. Prior work illustrates that intra-amniotic inflammation leads to an increase in TNFα at the fetal-maternal interface. In this study, pretreatment with a TNFα blockade partially reversed inflammation in the placental villi. Furthermore, we report that immune cells in the villous placenta sense LPS during our experimental window, and subsequently activate T cells to produce proinflammatory cytokines. Moreover, this study is the first report of memory T cells in the third trimester non-human primate placental villi and provides evidence that manipulation of immune cells in the villi at the fetal-maternal interface should be considered as a potential therapeutic target for intra-amniotic inflammation.