(159) Amnion Mesenchymal Macrophages: Characterization and Response to Infection

The primary organ of pregnancy, the placenta, exists as a maternal-fetal barrier and displays remarkable immunoactivity. However, the underlying mechanisms of immune regulation are not well understood. We previously identified the presence of CD14+ cells localized to the mesenchymal layer of the amnion, a distinct population of macrophages referred to as Amnion Mesenchymal Macrophages (AMMs). We hypothesize that these are regulated by the amnion and play a key role in pathogen clearance for S. agalactiae (GBS).

Study Design:

Fetal membranes were collected from cesarean sections in the absence of labor or inflammation. The amnion and chorion were cultured separately to generate conditioned media, and cytokine response was measured by ELISA. Sections of amnion were fixed for IF staining and imaged using a Nikon A1. Explants were infected using GBS and infectivity was quantified by CFUs.

Results:

Amnion explants have decreased colonization of GBS in comparison to chorion, intact fetal membrane, and chorionic villi. We found that the amnion secretes the cytokine IL-11 in greater abundance than chorion and chorionic villi. IL-11 secretion is responsive to TGFβ and colocalizes with AMMs. IL-11 secretion was reduced with treatment of cytochalasin D. Using conditioned media exposed to macrophages, we found that amnion conditioned macrophages (ACMs) have decreased infection with GBS suggesting that the secretory activity of the amnion regulates GBS clearance by macrophages. ACMs have decreased alpha-defensin and increased IL-11 production when exposed to GBS compared to chorion conditioned macrophages and chorionic villi conditioned macrophages.

Conclusion:

AMMs produce IL-11 and restrict GBS at the maternal-fetal interface. ACMs also restrict GBS, suggesting that they may function as a model for AMMs in vitro. Our data suggest that macrophage function at the maternal fetal interface is spatially distinct and tightly regulated. Further work elucidating the functional regulation of AMMs may provide insight into vertical transmission of pathogens across fetal membranes.