Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection
Monika I. Hollenhorst, … , Ulrich Boehm, Gabriela Krasteva-Christ
Monika I. Hollenhorst, … , Ulrich Boehm, Gabriela Krasteva-Christ
Published May 3, 2022
Citation Information: J Clin Invest. 2022;132(13):e150951. https://doi.org/10.1172/JCI150951.
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Research Article Immunology Pulmonology

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

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.

Authors

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 Munder, Sandra-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

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Figure 7

Evans blue (EB) extravasation and neutrophil recruitment in response to bacterial QSMs or bacterial culture supernatants.

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Evans blue (EB) extravasation and neutrophil recruitment in response to ...
(A, C, and E) Quantification of EB intensity in response to the QSMs N-(3-oxododecanoyl)-L-homoserine lactone (Oxo-HSL) and Pseudomonas aeruginosa quinolone signal (PQS) as well as supernatants of the P. aeruginosa strain NH57388A (NH) in WT (Trpm5+/+) and Trpm5-deficient (Trpm5–/–) mice. (B, D and F) Analysis of intra- and extraepithelial neutrophils per tracheal ring in WT (Trpm5+/+) and Trpm5–/– mice. In A–F, data are shown as single values ± SEM (n = 8–30 rings from 3–5 mice). *P < 0.05; **P < 0.01; ***P < 0.001 by 1-way ANOVA followed by Bonferroni’s multiple-comparison correction. (G) Proposed mechanism of induction of neurogenic inflammation after stimulation of the bitter signaling cascade in tracheal epithelial BCs with bitter or bacterial substances. Substances bind to bitter taste receptors, which activates α-gustducin, leading to Ca2+ release from intracellular stores that activates Trpm5 and ACh release from BCs. The released ACh then binds to ACh receptors on sensory neurons, leading to plasma extravasation and neutrophil recruitment via CGRP and SP release and to neurogenic inflammation.