Role of NOD2 in antiphospholipid antibody-induced and bacterial MDP amplification of trophoblast inflammation.

Overview

Women with antiphospholipid antibodies (aPL) are at high risk for pregnancy complications, such as preeclampsia. We previously demonstrated that aPL recognizing β₂GPI promote an extravillous trophoblast pro-inflammatory, anti-migratory and anti-angiogenic profile similar to that seen in preeclampsia. Since preeclampsia in the absence of aPL may have an underlying infectious element, women with aPL may be at increased risk for preeclampsia or other adverse outcomes if an infection is present. Our objective was to determine the impact the common bacterial component, muramyl dipeptide (MDP), has on trophoblast responses to aPL. Herein, we report that bacterial MDP amplifies trophoblast IL-1β expression, processing, and secretion in the presence of aPL through activation of NOD2. In the absence of MDP, NOD2 also mediates anti- β₂GPI antibody-induced trophoblast IL-1β and VEGF secretion. Additionally, we report a role for extravillous trophoblast vimentin as a novel danger signal that contributes to the aPL-induced trophoblast IL-1β production. Together our data indicate that NOD2 mediates trophoblast inflammatory and angiogenic responses to aPL alone, and mediates trophoblast inflammation in the presence of bacterial MDP. These findings suggest that a bacterial infection at the maternal-fetal interface may exacerbate the impact aPL have on trophoblast inflammation and, thus, on pregnancy outcome.