Anna-Lena Höbler, Andreas Ian Lackner, Barbara Öhler, Laszlo Musiejovsky, Peter Haslinger, Sigrid Vondra, Theresa Maxian, Felix Kosta, Gudrun Meinhardt, Jasmin Wächter, Patricia Favaro, Daniel Ho, Trevor Bruce, Hanna Waldhäusl, Leila Saleh, Christian Fiala, Sandra Haider, Gernot Schabbauer, Martin Knöfler, Sean C Bendall, Michael Angelo, Jürgen Pollheimer
Successful early pregnancy depends on coordinated interactions between the placenta and maternal immune cells, but the mechanisms underlying this interplay remain incompletely understood. Placenta-derived extravillous trophoblasts (EVTs) invade the decidua basalis and remodel maternal vessels, yet the contribution of neutrophils to this process is unclear. Here, we analyzed first-trimester human decidual tissue together with blood samples and identified decidual fibrinoid-associated neutrophils (dFANs) localized to Rohr's layer, a fibrinoid matrix between the decidua proper and the intervillous space. Flow cytometry and mass cytometry showed that dFANs differ phenotypically from donor-matched peripheral blood neutrophils (PBNs). Functionally, dFANs secreted high levels of matrix metalloproteinase-9 (MMP-9) and promoted EVT invasion, whereas PBNs induced EVT apoptosis. dFAN-derived MMP-9 enhanced activation of latent transforming growth factor-β (TGF-β), which suppressed PBN cytotoxicity and shifted PBNs toward an MMP-9-hypersecretory, proinvasive state. These findings define a dFAN-dependent MMP-9-TGF-β axis that supports invasive placentation at the maternal-fetal interface.