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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Neurol. | doi: 10.3389/fneur.2019.00307

Immediate neutrophil-variable-T cell receptor host response in bacterial meningitis

 Tina Fuchs1*, Kerstin Puellmann2, David H. Dreyfus3, Armin P. Piehler4, Björn Reuter5, Christopher Schwarzbach5, Olaf Willmann5, Diego Yepes1, Victor Costina1, Peter Findeisen1, Jens Mahrt6, Jian Han7, Chunlin Wang7, Alexander W. Beham8, Michael Neumaier1 and Wolfgang E. Kaminski4
  • 1Institut für Klinische Chemie, Medizinische Fakultät Mannheim, Universität Heidelberg, Germany
  • 2Aesculabor Hamburg, Germany
  • 3Department of Pediatrics, School of Medicine, Yale University, United States
  • 4Bioscientia, Germany
  • 5Neurologische Klinik, Universitätsmedizin Mannheim, Germany
  • 6Klinische Optische Mikroskopie, Universitätsmedizin Göttingen, Germany
  • 7iRepertoire inc., United States of America
  • 8Abteilung für Allgemein- und Viszeralchirurgie, Kreisklinikum Siegen, Germany

Bacterial meningitis is a life-threatening disease that evokes an intense neutrophil-dominated host response to microbes invading the subarachnoid space. Recent evidence indicates the existence of combinatorial V(D)J immune receptors in neutrophils that are based on the T cell receptor (TCR). Here, we investigated expression of the novel neutrophil TCRαβ-based V(D)J receptors in cerebrospinal fluid (CSF) from human patients with acute-phase bacterial meningitis using immunocytochemical, genetic immunoprofiling, cell biological and mass spectrometric techniques. We find that the human neutrophil combinatorial V(D)J receptors are rapidly induced in CSF neutrophils during the first hours of bacterial meningitis. Immune receptor repertoire diversity is consistently increased in CSF neutrophils relative to circulating neutrophils and phagocytosis of baits directed to the variable immunoreceptor is enhanced in CSF neutrophils during acute-phase meningitis. Our results reveal that a flexible immune response involving neutrophil V(D)J receptors which enhance phagocytosis is immediately initiated at the site of acute bacterial infection.

Keywords: Bacterial meningitis, T cell receptor (TCR), Neutrophil granulocytes, Phagocytosis, Variable immune receptor

Received: 11 Sep 2018; Accepted: 11 Mar 2019.

Edited by:

Steven Jacobson, National Institute of Neurological Disorders and Stroke (NINDS), United States

Reviewed by:

Jun Zhu, Mokobio Biotechnology R&D Center, Inc., United States
Lars-Ove Brandenburg, University Hospital RWTH Aachen, Germany  

Copyright: © 2019 Fuchs, Puellmann, Dreyfus, Piehler, Reuter, Schwarzbach, Willmann, Yepes, Costina, Findeisen, Mahrt, Han, Wang, Beham, Neumaier and Kaminski. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Tina Fuchs, Institut für Klinische Chemie, Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany,