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 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

doi:10.1172/JCI150951

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

Institute of Anatomy

36 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 language	English
Article number	e150951
Journal	Journal of Clinical Investigation
Volume	132
Issue number	13
ISSN	0021-9738
DOIs	https://doi.org/10.1172/JCI150951
Publication status	Published - 01.07.2022

Funding

The authors thank Ursula Roth (Julius-Maximilians-University); Nora Aouragh, Andrea Rabung, and Aline Herges (Saarland University); and Joanna Zaisserer (Ludwig-Maximilians-University) for skillful technical assistance, Philipp Wartenberg for slide scanning, Daniela Yildiz for the expert advice in FACS analysis, Stephan Max-einer (Saarland University) for critical reading of the manuscript, Lutz Wiehlmann (Hannover Medical School) for providing the P. aeruginosa strain D8A6, and Niels Hoiby (University of Copenhagen, Denmark) for providing the P. aeruginosa strain NH57388A. This work was supported by the German Research Foundation (DFG SFB TRR 152 projects P01 and Z02 to VF, projects P11 and Z02 to UB, project P14 to SZ, project P15 to VC and TG, project P17 to PL, project P22 to GKC, KR4338/1-2 to GKC, DFG Research Training Group 2338 to TG, SFB TR 84 projects C6 and C9 to MW, and PI 1084/4, PI 1084/5, TRR179 TP11, and TRR237 A07 to AP), by an ERC consolidator grant (ERC-CoG ProDAP, 817798 to AP), by the German Federal Ministry of Education and Research (BMBF) (e:Med CAPSyS-FKZ 01ZX1304B and 01ZX1604B, Phage-4Cure-FKZ 16GW0141, SYMPATH-FKZ 01ZX1906A to MW; DZL 82DZL001A2 to PK) and by the Agence nationale de la recherche and BMBF (MAPVAP-FKZ 16GW0247 to SMW and MW).

Research Areas and Centers

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

DFG Research Classification Scheme

2.21-05 Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Hollenhorst, M. I., Nandigama, R., Evers, S. B., Gamayun, I., Wadood, N. A., Salah, A., Pieper, M., Wyatt, A., Stukalov, A., Gebhardt, A., Nadolni, W., Burow, W., Herr, C., Beisswenger, C., Kusumakshi, S., Ectors, F., Kichko, T. I., Hübner, L., Reeh, P., ... Krasteva-Christ, G. (2022). Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection. Journal of Clinical Investigation, 132(13), Article e150951. https://doi.org/10.1172/JCI150951

@article{476a46e6714a455cb42445a635687f1c,

title = "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.",

author = "Hollenhorst, \{Monika I.\} and Rajender Nandigama and Evers, \{Saskia B.\} and Igor Gamayun and Wadood, \{Noran Abdel\} and Alaa Salah and Mario Pieper and Amanda Wyatt and Alexey Stukalov and Anna Gebhardt and Wiebke Nadolni and Wera Burow and Christian Herr and Christoph Beisswenger and Soumya Kusumakshi and Fabien Ectors and Kichko, \{Tatjana I.\} and Lisa H{\"u}bner and Peter Reeh and Antje Munder and Wienhold, \{Sandra Maria\} and Martin Witzenrath and Robert Bals and Veit Flockerzi and Thomas Gudermann and Markus Bischoff and Peter Lipp and Susanna Zierler and Vladimir Chubanov and Andreas Pichlmair and Peter K{\"o}nig and Ulrich Boehm and Gabriela Krasteva-Christ",

note = "Publisher Copyright: Copyright: {\textcopyright} 2022, Hollenhorst et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.",

year = "2022",

month = jul,

day = "1",

doi = "10.1172/JCI150951",

language = "English",

volume = "132",

journal = "Journal of Clinical Investigation",

issn = "0021-9738",

publisher = "American Society for Clinical Investigation",

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Hollenhorst, MI, Nandigama, R, Evers, SB, Gamayun, I, Wadood, NA, Salah, A, Pieper, M, Wyatt, A, Stukalov, A, Gebhardt, A, Nadolni, W, Burow, W, Herr, C, Beisswenger, C, Kusumakshi, S, Ectors, F, Kichko, TI, Hübner, L, Reeh, P, Munder, A, Wienhold, SM, Witzenrath, M, Bals, R, Flockerzi, V, Gudermann, T, Bischoff, M, Lipp, P, Zierler, S, Chubanov, V, Pichlmair, A, König, P, Boehm, U & Krasteva-Christ, G 2022, 'Bitter taste signaling in tracheal epithelial brush cells elicits innate immune responses to bacterial infection', Journal of Clinical Investigation, vol. 132, no. 13, e150951. https://doi.org/10.1172/JCI150951

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

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 - https://www.scopus.com/pages/publications/85133697633

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 -

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

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

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