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  3. Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion

Stroke and myocardial infarction induce neutrophil extracellular trap release disrupting lymphoid organ structure and immunoglobulin secretion

  • Nat Cardiovasc Res. 2024 May;3(5):525-540. doi: 10.1038/s44161-024-00462-8.
Ali A Tuz 1,  Susmita Ghosh 2,  Laura Karsch 1,  Dimitris Ttoouli 3,  Sai P Sata 2,  Özgür Ulusoy 1,  Andreas Kraus 1,  Nils Hoerenbaum 1,  Jan-Niklas Wolf 1,  Sabrina Lohmann 1,  Franziska Zwirnlein 1,  Viola Kaygusuz 1,  Vivian Lakovic 1,  Hannah-Lea Tummes 1,  Alexander Beer 1,  Markus Gallert 1,  Stephanie Thiebes 4,  Altea Qefalia 1,  Zülal Cibir 1,  Medina Antler 1,  Sebastian Korste 5,  Elias Haj Yehia 5,  Lars Michel 5,  Tienush Rassaf 5,  Britta Kaltwasser 6,  Hossam Abdelrahman 1,  Ayan Mohamud Yusuf 6,  Chen Wang 6,  Dongpei Yin 6,  Lars Haeusler 1,  Smiths Lueong 7,  Mathis Richter 8,  Daniel R Engel 4,  Martin Stenzel 2,  Oliver Soehnlein 8,  Benedikt Frank 6,  Mialitiana Solo-Nomenjanahary 9,  Benoît Ho-Tin-Noé 9,  Jens T Siveke 7,  Matthias Totzeck 5,  Daniel Hoffmann 3,  Anika Grüneboom 2,  Nina Hagemann 6,  Anja Hasenberg 1,  Jean-Philippe Desilles 9 10,  Mikael Mazighi 9 10,  Albert Sickmann 2 11 12,  Jianxu Chen 2,  Dirk M Hermann 6,  Matthias Gunzer 13 14,  Vikramjeet Singh 15
Affiliations

Affiliations

  • 1 Institute for Experimental Immunology and Imaging, University Hospital, University of Duisburg-Essen, Essen, Germany.
  • 2 Leibniz-Institut für Analytische Wissenschaften - ISAS-e.V., Dortmund, Germany.
  • 3 Bioinformatics and Computational Biophysics, Faculty of Biology and Centre for Medical Biotechnology (ZMB), University of Duisburg-Essen, Essen, Germany.
  • 4 Department of Immunodynamics, Institute of Experimental Immunology and Imaging, University Hospital Essen, Essen, Germany.
  • 5 Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, University Hospital, University of Duisburg-Essen, Essen, Germany.
  • 6 Department of Neurology, University Hospital, University of Duisburg-Essen, Essen, Germany.
  • 7 Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK, partner site Essen), German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 8 Institute for Experimental Pathology (ExPat), Center for Molecular Biology of Inflammation (ZMBE), Universität Münster, Münster, Germany.
  • 9 Optimisation Thérapeutique en Neuropsychopharmacologie, Université Paris Cité, U1144 Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France.
  • 10 Interventional Neuroradiology Department and Biological Resources Center, Rothschild Foundation Hospital, Paris, France.
  • 11 Medizinisches Proteom-Center, Ruhr-Universität Bochum, Bochum, Germany.
  • 12 Department of Chemistry, College of Physical Sciences, University of Aberdeen, Aberdeen, UK.
  • 13 Institute for Experimental Immunology and Imaging, University Hospital, University of Duisburg-Essen, Essen, Germany. [email protected].
  • 14 Leibniz-Institut für Analytische Wissenschaften - ISAS-e.V., Dortmund, Germany. [email protected].
  • 15 Institute for Experimental Immunology and Imaging, University Hospital, University of Duisburg-Essen, Essen, Germany. [email protected].
PMID: 39195931 DOI: 10.1038/s44161-024-00462-8
Abstract

Post-injury dysfunction of humoral immunity accounts for infections and poor outcomes in cardiovascular diseases. Among immunoglobulins (Ig), IgA, the most abundant mucosal antibody, is produced by plasma B cells in intestinal Peyer's patches (PP) and lamina propria. Here we show that patients with stroke and myocardial ischemia (MI) had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid loss of IgA-producing plasma cells in PP and lamina propria. Reduced plasma IgG was detectable in patients and experimental mice 3-10 d after injury. Stroke/MI triggered the release of neutrophil extracellular traps (NETs). Depletion of neutrophils, NET degradation or blockade of NET release inhibited the loss of IgA+ cells and circulating IgA in experimental stroke and MI and in patients with stroke. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological Ig secretion and how this can be inhibited in patients.

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