Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection.

Autor: Hollenhorst MI; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany., Nandigama R; Institute of Anatomy and Cell Biology, Julius-Maximilians-University, Würzburg, Germany., Evers SB; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany., Gamayun I; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany., Abdel Wadood N; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany., Salah A; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany., Pieper M; Institute of Anatomy, University of Lübeck, and Airway Research Center North (ARCN), Lübeck, Germany.; German Center for Lung Research (DZL), Germany., Wyatt A; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany., Stukalov A; Immunopathology of Virus Infections Laboratory, Institute of Virology, School of Medicine, Technical University of Munich, Munich, Germany., Gebhardt A; Immunopathology of Virus Infections Laboratory, Institute of Virology, School of Medicine, Technical University of Munich, Munich, Germany., Nadolni W; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany., Burow W; Institute of Anatomy and Cell Biology, Julius-Maximilians-University, Würzburg, Germany., Herr C; Department of Internal Medicine V-Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany., Beisswenger C; Department of Internal Medicine V-Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany., Kusumakshi S; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany., Ectors F; FARAH Mammalian Transgenics Platform, Liège University, Liège, Belgium., Kichko TI; Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany., Hübner L; Institute of Anatomy and Cell Biology, Julius-Maximilians-University, Würzburg, Germany., Reeh P; Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany., Munder A; German Center for Lung Research (DZL), Germany.; Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, and Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany., Wienhold SM; Department of Infectious Diseases and Respiratory Medicine and Division of Pulmonary Inflammation, Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany., Witzenrath M; Department of Infectious Diseases and Respiratory Medicine and Division of Pulmonary Inflammation, Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany., Bals R; Department of Internal Medicine V-Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany., Flockerzi V; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany.; Center for Molecular Signaling., Gudermann T; German Center for Lung Research (DZL), Germany.; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany., Bischoff M; Institute for Medical Microbiology and Hygiene, and., Lipp P; Department of Infectious Diseases and Respiratory Medicine and Division of Pulmonary Inflammation, Charité - University Medicine Berlin, corporate member of Free University Berlin and Humboldt-University Berlin, Berlin, Germany.; Institute for Molecular Cell Biology and Research Center for Molecular Imaging and Screening, Saarland University, Homburg, Germany., Zierler S; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany.; Institute of Pharmacology, Johannes Kepler University Linz, Linz, Austria., Chubanov V; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany., Pichlmair A; Immunopathology of Virus Infections Laboratory, Institute of Virology, School of Medicine, Technical University of Munich, German Center for Infection Research (DZIF), Munich, Germany., König P; Institute of Anatomy, University of Lübeck, and Airway Research Center North (ARCN), Lübeck, Germany.; German Center for Lung Research (DZL), Germany., Boehm U; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany.; Center for Molecular Signaling., Krasteva-Christ G; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany.
Jazyk: angličtina
Zdroj: The Journal of clinical investigation [J Clin Invest] 2022 Jul 01; Vol. 132 (13).
DOI: 10.1172/JCI150951
Abstrakt: Constant exposure of the airways to inhaled pathogens requires efficient early immune responses protecting against infections. How bacteria on the epithelial surface are detected and first-line protective mechanisms are initiated are not well understood. We have recently shown that tracheal brush cells (BCs) express functional taste receptors. Here we report that bitter taste signaling in murine BCs induces neurogenic inflammation. We demonstrate that BC signaling stimulates adjacent sensory nerve endings in the trachea to release the neuropeptides CGRP and substance P that mediate plasma extravasation, neutrophil recruitment, and diapedesis. Moreover, we show that bitter tasting quorum-sensing molecules from Pseudomonas aeruginosa activate tracheal BCs. BC signaling depends on the key taste transduction gene Trpm5, triggers secretion of immune mediators, among them the most abundant member of the complement system, and is needed to combat P. aeruginosa infections. Our data provide functional insight into first-line defense mechanisms against bacterial infections of the lung.
Databáze: MEDLINE