Fibrinoid-associated neutrophils promote invasive placentation and neutrophil reprogramming at the maternal-fetal interface
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.
Authors
- Michael R. Angelo (ORCID: https://orcid.org/0000-0003-1531-5067)
- Sandra Haider (ORCID: https://orcid.org/0000-0003-2409-1317)
- Jasmin Wächter (ORCID: https://orcid.org/0000-0003-2422-5389)
- Felix Kosta
- Andreas Ian Lackner (ORCID: https://orcid.org/0000-0002-8034-0181)
- Trevor Bruce
- Anna-Lena Höbler (ORCID: https://orcid.org/0000-0001-5529-9378)
- Gernot Schabbauer (ORCID: https://orcid.org/0000-0002-7490-8009)
- Barbara Öhler
- Laszlo Musiejovsky (ORCID: https://orcid.org/0009-0002-9238-4752)
- Sean C. Bendall (ORCID: https://orcid.org/0000-0003-1341-2453)
- Gudrun Meinhardt (ORCID: https://orcid.org/0000-0002-8115-8867)
- Sigrid Vondra (ORCID: https://orcid.org/0000-0003-0206-8319)
- Jürgen Pollheimer (ORCID: https://orcid.org/0000-0001-8440-5221)
- Theresa Maxian (ORCID: https://orcid.org/0000-0002-8009-8479)
- Christian Fiala (ORCID: https://orcid.org/0000-0001-6451-7349)
- Hanna Waldhäusl (ORCID: https://orcid.org/0009-0003-6595-3558)
- Peter Haslinger (ORCID: https://orcid.org/0000-0003-1408-7584)
- Daniel Ho
- Patricia M.B. Favaro (ORCID: https://orcid.org/0000-0002-3764-9538)
- Leila Saleh
- Martin Knöfler
Institutions
- Karolinska Institutet (SE)
- Medical University of Vienna (AT)
- Stanford University (US)
Publication Details
- Journal
- Science Immunology
- Published
- 2026-09-25
- DOI
- https://doi.org/10.1126/sciimmunol.aea4118
- Primary Topic
- Pregnancy and preeclampsia studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00