AUTHOR=Fuchs Tina , Puellmann Kerstin , Dreyfus David H. , Piehler Armin P. , Reuter Björn , Schwarzbach Christopher , Willmann Olaf , Yepes Diego , Costina Victor , Findeisen Peter , Mahrt Jens , Wang Chunlin , Han Jian , Beham Alexander W. , Neumaier Michael , Kaminski Wolfgang E. TITLE=Immediate Neutrophil-Variable-T Cell Receptor Host Response in Bacterial Meningitis JOURNAL=Frontiers in Neurology VOLUME=10 YEAR=2019 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.00307 DOI=10.3389/fneur.2019.00307 ISSN=1664-2295 ABSTRACT=

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.