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 1

Measurements of intracellular calcium levels in Trpm5-GCaMP3 cells.

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Measurements of intracellular calcium levels in Trpm5-GCaMP3 cells. (A a...
(A and B) Immunohistochemical staining of tracheal sections from a Trpm5-tauGFP (A and B) or Chat-eGFP (C and D) mouse using an antiserum against Trpm5. L, lumen; E, epithelium; LP, lamina propria. (E) Image of the trachea of a Trpm5-GCaMP3 mouse showing an increase in GCaMP3 fluorescence in individual Trpm5+ cells after denatonium application (20 mM). Scale bars: 50 μm (A–D) and 20 μm (E). (F) Graphs showing Ca2+ transients of Trpm5+ tracheal cells from Trpm5-GCaMP3 mice responding to 1, 10, or 20 mM denatonium applied at 180 seconds (left, central, and right graph, respectively). Data shown as mean ± SEM of the normalized (F/F0) GCaMP3 fluorescence intensities. Red line shows the initial (start recording, t = 0, F/F0 = 1) level of the normalized intensities. n cells = 23 from 3 mice. (G) Representative curve for the Ca2+ response of a Trpm5+ cell stimulated with 1 mM N-(3-oxododecanoyl)-L-homoserine lactone (Oxo). Images of the Trpm5+ cell show GCaMP3 baseline fluorescence and fluorescence after stimulation. (H) Oxo (1 mM) led to a significant transient increase in [Ca2+]i in Trpm5+ cells from Trpm5-GCaMP3 mouse tracheae. Data shown as single values and mean ± SEM of the normalized (F/F0) GCaMP3 fluorescence intensities (n cells = 10 from 3 mice). **P < 0.01 by 2-tailed, unpaired Student’s t test. (I) Representative curve for the Ca2+ response of Trpm5+ cells to 1, 10, or 50 μM Pseudomonas aeruginosa quinolone signal (PQS) (1 μM: n cells = 28 from 3 tracheal pieces; 10 μM: n cells = 30 from 3 tracheal pieces; 50 μM: n cells = 40 from 4 tracheal pieces).