TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Hollenhorst, Monika I.
A1  - Jurastow, Innokentij
A1  - Nandigama, Rajender
A1  - Appenzeller, Silke
A1  - Li, Lei
A1  - Vogel, Joerg
A1  - Wiederhold, Stephanie
A1  - Althaus, Mike
A1  - Empting, Martin
A1  - Altmueller, Janine
A1  - Hirsch, Anna K. H.
A1  - Flockerzi, Veit
A1  - Canning, Brendan J.
A1  - Saliba, Antoine-Emmanuel
A1  - Krasteva-Christ, Gabriela
T1  - Tracheal brush cells release acetylcholine in response to bitter tastants for paracrine and autocrine signaling
JF  - The FASEB Journal
N2  - 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.
KW  - taste
KW  - single-cell RNA-seq
KW  - mucociliary clearance
KW  - acetylcholine
KW  - brush cells
SN  - 0892-6638
SS  - 0892-6638
U6  - https://doi.org/10.1096/fj.201901314RR
DO  - https://doi.org/10.1096/fj.201901314RR
PM  - 31914675
VL  - 34
IS  - 1
SP  - 316
EP  - 332
S1  - 17
PB  - Federation of American Societies for Experimental Biology
ER  -