Immunology; Innate immunity; Pulmonology; General Medicine
Abstract :
[en] 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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Hollenhorst, Monika I; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany
Nandigama, Rajender ; Institute of Anatomy and Cell Biology, Julius-Maximilians-University, Würzburg, Germany
Evers, Saskia B; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany
Gamayun, Igor; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany
Abdel Wadood, Noran; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany
Salah, Alaa ; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany
Pieper, Mario ; Institute of Anatomy, University of Lübeck, and Airway Research Center North (ARCN), Lübeck, Germany ; German Center for Lung Research (DZL), Germany
Wyatt, Amanda; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany
Stukalov, Alexey ; Immunopathology of Virus Infections Laboratory, Institute of Virology, School of Medicine, Technical University of Munich, Munich, Germany
Gebhardt, Anna; Immunopathology of Virus Infections Laboratory, Institute of Virology, School of Medicine, Technical University of Munich, Munich, Germany
Nadolni, Wiebke; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany
Burow, Wera; Institute of Anatomy and Cell Biology, Julius-Maximilians-University, Würzburg, Germany
Herr, Christian ; Department of Internal Medicine V-Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany
Beisswenger, Christoph ; Department of Internal Medicine V-Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany
Kusumakshi, Soumya; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany
Ectors, Fabien ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Kichko, Tatjana I ; Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
Hübner, Lisa; Institute of Anatomy and Cell Biology, Julius-Maximilians-University, Würzburg, Germany
Reeh, Peter ; Institute of Physiology and Pathophysiology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
Munder, Antje; 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, Sandra-Maria; 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, Martin ; 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, Robert; Department of Internal Medicine V-Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany
Flockerzi, Veit; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany ; Center for Molecular Signaling
Gudermann, Thomas ; German Center for Lung Research (DZL), Germany ; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany
Bischoff, Markus ; Institute for Medical Microbiology and Hygiene, and
Lipp, Peter ; 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, Susanna ; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany ; Institute of Pharmacology, Johannes Kepler University Linz, Linz, Austria
Chubanov, Vladimir ; Walther-Straub-Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University, Munich, Germany
Pichlmair, Andreas ; Immunopathology of Virus Infections Laboratory, Institute of Virology, School of Medicine, Technical University of Munich, German Center for Infection Research (DZIF), Munich, Germany
König, Peter; Institute of Anatomy, University of Lübeck, and Airway Research Center North (ARCN), Lübeck, Germany ; German Center for Lung Research (DZL), Germany
Boehm, Ulrich; Institute for Experimental and Clinical Pharmacology and Toxicology, Saarland University, School of Medicine, Homburg, Germany ; Center for Molecular Signaling
Krasteva-Christ, Gabriela; Institute of Anatomy and Cell Biology, Saarland University, School of Medicine, Homburg, Germany
DFG - Deutsche Forschungsgemeinschaft [DE] ERC - European Research Council [BE] BMBF - Bundesministerium für Bildung und Forschung [DE] ANR - Agence Nationale de la Recherche [FR]
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