Chemosensory Cell-Derived Acetylcholine Drives Tracheal Mucociliary Clearance in Response to Virulence-Associated Formyl Peptides.

Autor:	Perniss A; Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, 35385 Giessen, Germany., Liu S; Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany; Department of Medicine III, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany., Boonen B; Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany., Keshavarz M; Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, 35385 Giessen, Germany., Ruppert AL; Institute of Anatomy and Cell Biology, Philipps-University, 35037 Marburg, Germany., Timm T; Institute of Biochemistry, Justus Liebig University, 35385 Giessen, Germany., Pfeil U; Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, 35385 Giessen, Germany., Soultanova A; Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, 35385 Giessen, Germany., Kusumakshi S; Experimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany., Delventhal L; Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, 35385 Giessen, Germany., Aydin Ö; Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, 35385 Giessen, Germany., Pyrski M; Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany., Deckmann K; Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, 35385 Giessen, Germany., Hain T; Institute of Medical Microbiology, German Center for Infection Research, Justus Liebig University, 35385 Giessen, Germany., Schmidt N; Institute of Hygiene and Infectious Diseases of Animals, Justus Liebig University, 35392 Giessen, Germany., Ewers C; Institute of Hygiene and Infectious Diseases of Animals, Justus Liebig University, 35392 Giessen, Germany., Günther A; Center for Interstitial and Rare Lung Diseases, Department of Internal Medicine, German Center for Lung Research, Justus Liebig University, 35385 Giessen, Germany; Agaplesion Lung Clinic Waldhof-Elgershausen, 35753 Greifenstein, Germany., Lochnit G; Institute of Biochemistry, Justus Liebig University, 35385 Giessen, Germany., Chubanov V; Walther-Straub Institute of Pharmacology and Toxicology, German Center for Lung Research, Ludwig-Maximilians-Universität München, 80336 Munich, Germany., Gudermann T; Walther-Straub Institute of Pharmacology and Toxicology, German Center for Lung Research, Ludwig-Maximilians-Universität München, 80336 Munich, Germany., Oberwinkler J; Institute of Physiology and Pathophysiology, Philipps-University, 35037 Marburg, Germany., Klein J; Department of Pharmacology and Clinical Pharmacy, FB14, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany., Mikoshiba K; Laboratory of Cell Calcium Signaling, Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, 201210 Shanghai, China., Leinders-Zufall T; Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany., Offermanns S; Department of Pharmacology, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany., Schütz B; Institute of Anatomy and Cell Biology, Philipps-University, 35037 Marburg, Germany., Boehm U; Experimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland University, 66421 Homburg, Germany., Zufall F; Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany., Bufe B; Center for Integrative Physiology and Molecular Medicine, Saarland University, 66421 Homburg, Germany; Department of Informatics and Microsystems Technology, University of Applied Sciences, 67659 Kaiserslautern, Germany., Kummer W; Institute for Anatomy and Cell Biology, German Center for Lung Research, Justus Liebig University, 35385 Giessen, Germany. Electronic address: wolfgang.kummer@anatomie.med.uni-giessen.de.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2020 Apr 14; Vol. 52 (4), pp. 683-699.e11.
DOI:	10.1016/j.immuni.2020.03.005
Abstrakt:	Mucociliary clearance through coordinated ciliary beating is a major innate defense removing pathogens from the lower airways, but the pathogen sensing and downstream signaling mechanisms remain unclear. We identified virulence-associated formylated bacterial peptides that potently stimulated ciliary-driven transport in the mouse trachea. This innate response was independent of formyl peptide and taste receptors but depended on key taste transduction genes. Tracheal cholinergic chemosensory cells expressed these genes, and genetic ablation of these cells abrogated peptide-driven stimulation of mucociliary clearance. Trpm5-deficient mice were more susceptible to infection with a natural pathogen, and formylated bacterial peptides were detected in patients with chronic obstructive pulmonary disease. Optogenetics and peptide stimulation revealed that ciliary beating was driven by paracrine cholinergic signaling from chemosensory to ciliated cells operating through muscarinic M3 receptors independently of nerves. We provide a cellular and molecular framework that defines how tracheal chemosensory cells integrate chemosensation with innate defense. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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