Proteoglycofili are glycosaminoglycan-containing fibrillar components released by neutrophils to neutralize bacteria
Here, we uncover that neutrophils release a fibrillar complex, named proteoglycofili (PGF), under hypoxic conditions or upon bacterial infection, using Shigella as a model. PGF are preferentially released by neutrophils over neutrophil extracellular traps upon bacterial infection. PGF are released by living neutrophils, do not contain DNA, are mainly composed of granule proteins, and contain cytokines. We reveal that the fibrillar structure of PGF is sustained by two glycosaminoglycans (GAGs), hyaluronic acid, and chondroitin sulfate, released by neutrophils. We demonstrate that PGF are potent antimicrobials, which degrade virulence factors of Shigella and block its growth, similar to E. coli or Salmonella. GAGs are essential for PGF antimicrobial activity both in vitro and in vivo. Beyond bacterial infections, and reported in a mouse model of colon cancer, our results strongly suggest that GAGs may be released by neutrophils in a broad range of inflammatory diseases.
Authors
- Marina Valente Barroso (ORCID: https://orcid.org/0000-0001-8135-9100)
- Caroline Ridley (ORCID: https://orcid.org/0000-0002-5483-0320)
- Ahmad Sabbah (ORCID: https://orcid.org/0000-0002-5915-4720)
- Stéphane Rigaud (ORCID: https://orcid.org/0000-0003-2161-0927)
- Antonin C. André (ORCID: https://orcid.org/0000-0001-7015-4791)
- David J. Thornton (ORCID: https://orcid.org/0000-0001-7148-1970)
- Katia Boniface (ORCID: https://orcid.org/0000-0003-4428-1222)
- Isabelle Svahn (ORCID: https://orcid.org/0000-0001-5738-3194)
- Lorine Debande (ORCID: https://orcid.org/0000-0003-2043-8707)
- Romain R. Vivès (ORCID: https://orcid.org/0000-0003-4295-5449)
- Amber D. Bowler (ORCID: https://orcid.org/0000-0002-9439-2839)
- J. P. Tritschler
- Benoît Marteyn (ORCID: https://orcid.org/0000-0001-5638-702X)
- Freddy Radtke (ORCID: https://orcid.org/0000-0003-4315-4045)
- Jean-Yves Tinévez (ORCID: https://orcid.org/0000-0002-0998-4718)
- Valérie Demais (ORCID: https://orcid.org/0000-0003-1328-1115)
- Jūratė Skerniškytė (ORCID: https://orcid.org/0000-0002-6301-4181)
- Mélina Siegwald
- Philippe J. Sansonetti
- Vanessa Paul
- Nathan Broussaudier
Institutions
- Centre National de la Recherche Scientifique (FR)
- Université de Bordeaux (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- Wellcome Centre for Cell-Matrix Research (GB)
- University of Manchester (GB)
- CEA Grenoble (FR)
- Bordeaux Population Health (FR)
- Immunology from Concept and Experiments to Translation (FR)
- Institut d'Etudes Avancées Paris (FR)
- Architecture et Réactivité de l'arN (FR)
- Laboratoire Image, Ville, Environnement (FR)
- Institut de Biologie Structurale (FR)
- Institut de Biologie Moléculaire et Cellulaire (FR)
- Pathogenèse des infections vasculaires
- Bordeaux Imaging Center (FR)
- École Polytechnique Fédérale de Lausanne (CH)
- Université de Strasbourg (FR)
- Université Grenoble Alpes (FR)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116541
- Primary Topic
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00