Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection

Monika I. Hollenhorst, Rajender Nandigama, Saskia B. Evers, Igor Gamayun, Noran Abdel Wadood, Alaa Salah, Mario Pieper, Amanda Wyatt, Alexey Stukalov, Anna Gebhardt, Wiebke Nadolni, Wera Burow, Christian Herr, Christoph Beisswenger, Soumya Kusumakshi, Fabien Ectors, Tatjana I. Kichko, Lisa Hübner, Peter Reeh, Antje MunderSandra Maria Wienhold, Martin Witzenrath, Robert Bals, Veit Flockerzi, Thomas Gudermann, Markus Bischoff, Peter Lipp, Susanna Zierler, Vladimir Chubanov, Andreas Pichlmair, Peter König, Ulrich Boehm, Gabriela Krasteva-Christ*

*Corresponding author for this work
14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere150951
JournalJournal of Clinical Investigation
Volume132
Issue number13
ISSN0021-9738
DOIs
Publication statusPublished - 01.07.2022

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

  • 204-05 Immunology

Cite this