Hollenhorst, Monika I., Jurastow, Innokentij, Nandigama, Rajender ORCID: 0000-0002-7344-4732, Appenzeller, Silke, Li, Lei, Vogel, Joerg, Wiederhold, Stephanie, Althaus, Mike ORCID: 0000-0002-3554-7538, Empting, Martin, Altmueller, Janine, Hirsch, Anna K. H., Flockerzi, Veit, Canning, Brendan J., Saliba, Antoine-Emmanuel and Krasteva-Christ, Gabriela ORCID: 0000-0002-0113-521X (2020). Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling. Faseb J., 34 (1). S. 316 - 333. BETHESDA: FEDERATION AMER SOC EXP BIOL. ISSN 1530-6860

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Abstract

For protection from inhaled pathogens many strategies have evolved in the airways such as mucociliary clearance and cough. We have previously shown that protective respiratory reflexes to locally released bacterial bitter taste substances are most probably initiated by tracheal brush cells (BC). Our single-cell RNA-seq analysis of murine BC revealed high expression levels of cholinergic and bitter taste signaling transcripts (Tas2r108, Gnat3, Trpm5). We directly demonstrate the secretion of acetylcholine (ACh) from BC upon stimulation with the Tas2R agonist denatonium. Inhibition of the taste transduction cascade abolished the increase in [Ca2+](i) in BC and subsequent ACh-release. ACh-release is regulated in an autocrine manner. While the muscarinic ACh-receptors M3R and M1R are activating, M2R is inhibitory. Paracrine effects of ACh released in response to denatonium included increased [Ca2+](i) in ciliated cells. Stimulation by denatonium or with Pseudomonas quinolone signaling molecules led to an increase in mucociliary clearance in explanted tracheae that was Trpm5- and M3R-mediated. We show that ACh-release from BC via the bitter taste cascade leads to immediate paracrine protective responses that can be boosted in an autocrine manner. This mechanism represents the initial step for the activation of innate immune responses against pathogens in the airways.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Hollenhorst, Monika I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jurastow, InnokentijUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nandigama, RajenderUNSPECIFIEDorcid.org/0000-0002-7344-4732UNSPECIFIED
Appenzeller, SilkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, LeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogel, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiederhold, StephanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Althaus, MikeUNSPECIFIEDorcid.org/0000-0002-3554-7538UNSPECIFIED
Empting, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Altmueller, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hirsch, Anna K. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Flockerzi, VeitUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canning, Brendan J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Saliba, Antoine-EmmanuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krasteva-Christ, GabrielaUNSPECIFIEDorcid.org/0000-0002-0113-521XUNSPECIFIED
URN: urn:nbn:de:hbz:38-352123
DOI: 10.1096/fj.201901314RR
Journal or Publication Title: Faseb J.
Volume: 34
Number: 1
Page Range: S. 316 - 333
Date: 2020
Publisher: FEDERATION AMER SOC EXP BIOL
Place of Publication: BETHESDA
ISSN: 1530-6860
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CHOLINERGIC CHEMOSENSORY CELLS; TUFT CELLS; TASTE; RECEPTORS; MECHANISM; TRIGGERS; IMMUNITY; CILIA; MICEMultiple languages
Biochemistry & Molecular Biology; Biology; Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/35212

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