TY - JOUR
T1 - Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection
AU - Hollenhorst, Monika I.
AU - Nandigama, Rajender
AU - Evers, Saskia B.
AU - Gamayun, Igor
AU - Wadood, Noran Abdel
AU - Salah, Alaa
AU - Pieper, Mario
AU - Wyatt, Amanda
AU - Stukalov, Alexey
AU - Gebhardt, Anna
AU - Nadolni, Wiebke
AU - Burow, Wera
AU - Herr, Christian
AU - Beisswenger, Christoph
AU - Kusumakshi, Soumya
AU - Ectors, Fabien
AU - Kichko, Tatjana I.
AU - Hübner, Lisa
AU - Reeh, Peter
AU - Munder, Antje
AU - Wienhold, Sandra Maria
AU - Witzenrath, Martin
AU - Bals, Robert
AU - Flockerzi, Veit
AU - Gudermann, Thomas
AU - Bischoff, Markus
AU - Lipp, Peter
AU - Zierler, Susanna
AU - Chubanov, Vladimir
AU - Pichlmair, Andreas
AU - König, Peter
AU - Boehm, Ulrich
AU - Krasteva-Christ, Gabriela
N1 - Publisher Copyright:
Copyright: © 2022, Hollenhorst et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
PY - 2022/7/1
Y1 - 2022/7/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85133697633&partnerID=8YFLogxK
U2 - 10.1172/JCI150951
DO - 10.1172/JCI150951
M3 - Journal articles
C2 - 35503420
AN - SCOPUS:85133697633
SN - 0021-9738
VL - 132
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 13
M1 - e150951
ER -