Infection-induced preterm delivery involves a pro-inflammatory state, but not macrophage M2-M1 polarization, at the maternal-fetal interface (HUM8P.334)

Abstract

Objective: Endotoxin treatment causes preterm delivery in mice, and this is associated with an expansion of regulatory T cells (Tregs) in primary lymphoid organs (Arenas-Hernandez et al. unpublished data). Our aim was to determine whether this expansion causes a pro-inflammatory state and/or macrophage M2-M1 polarization at the maternal-fetal interface. Methods: Pregnant C57BL/6 mice were injected with either 15 μg of LPS (E. coli 0111:B4) or 200 μl PBS as a control (n=9-11 each). Mice were euthanized just prior to preterm delivery. Uterine and decidual cell suspensions were prepared and analyzed by flow cytometry to identify CD4+ and CD8+ Tregs, Th9 cells, Th17 cells, T-bet+ T cells, neutrophils, macrophages, IL4- and IFNγ-producing T cells, and M1 and M2 macrophages. Results: 1) Uterine, but not decidual, CD4+ Tregs were fewer in LPS treated mice than in controls (p=0.019); 2) Uterine and decidual macrophages were fewer in LPS treated mice than in controls (p=0.025 and 0.036); 3) Uterine and decidual neutrophils were greater in LPS treated mice than in controls (p=0.002 and 0.0001); 4) Decidual IFNγ-producing T cells were fewer in LPS treated mice than in controls (p=0.036); 5) M1 and M2 macrophage populations did not change with LPS treatment. Conclusions: Endotoxin treatment of pregnant mice promotes a pro-inflammatory stage, which includes abundant neutrophils and scarce regulatory T cells and macrophages (M1 and M2) at the maternal-fetal interface.