1. Neutrophils degranulate GAG-containing proteoglycofili, which block Shigella growth and degrade virulence factors
- Author
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Antonin C André, Marina Valente Barroso, Jurate Skerniskyte, Mélina Siegwald, Vanessa Paul, Lorine Debande, Caroline Ridley, Isabelle Svahn, Stéphane Rigaud, Jean-Yves Tinevez, Romain R Vivès, Philippe J Sansonetti, David J Thornton, Benoit S Marteyn, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Cité (UPCité), University of Manchester [Manchester], Bordeaux Imaging Center (BIC), Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagopole (CITECH), Institut Pasteur [Paris] (IP), CEA Grenoble (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP), Institut d’Etudes Avancées de l’Université de Strasbourg - Institute for Advanced Study (USIAS), Université de Strasbourg (UNISTRA), Pathogénèse des Infections vasculaires / Pathogenesis of Vascular Infections, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Tinevez, Jean-Yves
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] - Abstract
Summary paragraphNeutrophil degranulation plays a central role in their ability to kill pathogens but also to stimulate other immune cells1–3. Here we show that neutrophil degranulation, induced in hypoxia or upon Shigella infection in vitro and in vivo, leads to the release of polymers called neutrophil Proteoglycofili (PGF). PGF are mainly composed of granular proteins (myeloperoxidase, elastase, lactoferrin, cathelicidin, albumin) pre-stored in various types of granules, and chondroitin sulfate. PGF individual fibers have a diameter of 43.9 ± 20.3 nm and. They secreted by viable neutrophils and do not contain DNA, as opposed to NETs which contains also granular proteins, chondroitin sulfate in addition to chromatin, released upon neutrophil disintegration and cell death.We demonstrated that PGF block the growth of Shigella and other bacteria and degrade Shigella virulence factors. The degradation of the chondroitin sulfate polymers with testes hyaluronidases destabilizes PGF ultrastructure and abolishes its antimicrobial activity. Our results provide novel insights in the neutrophil degranulation process and open new doors for the investigation of PGF contribution to cytokines concentration gradient formation and adaptive immune cells activation. Further investigations are required to better appreciate the importance of this “sterile blaster” in infectious or inflammatory diseases.
- Published
- 2022