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A succinate/SUCNR1-brush cell defense program in the tracheal epithelium

  • Host-derived succinate accumulates in the airways during bacterial infection. Here, we show that luminal succinate activates murine tracheal brush (tuft) cells through a signaling cascade involving the succinate receptor 1 (SUCNR1), phospholipase Cβ2, and the cation channel transient receptor potential channel subfamily M member 5 (TRPM5). Stimulated brush cells then trigger a long-range Ca2+ wave spreading radially over the tracheal epithelium through a sequential signaling process. First, brush cells release acetylcholine, which excites nearby cells via muscarinic acetylcholine receptors. From there, the Ca2+ wave propagates through gap junction signaling, reaching also distant ciliated and secretory cells. These effector cells translate activation into enhanced ciliary activity and Cl- secretion, which are synergistic in boosting mucociliary clearance, the major innate defense mechanism of the airways. Our data establish tracheal brush cells as a central hub in triggering a global epithelial defense program in response to a danger-associated metabolite.

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Document Type:Article
Author:Alexander Perniss, Brett Boonen, Sarah Tonack, Moritz Thiel, Krupali Poharkar, Mohamad Wessam Alnouri, Maryam Keshavarz, Tamara Papadakis, Silke Wiegand, Uwe Pfeil, Katrin Richter, Mike Althaus, Johannes Oberwinkler, Burkhard Schütz, Ulrich Boehm, Stefan Offermanns, Trese Leinders-Zufall, Frank Zufall, Wolfgang Kummer
Parent Title (English):Science Advances
Article Number:eadg8842
Number of pages:20
Publisher:American Association for the Advancement of Science
Publishing Institution:Hochschule Bonn-Rhein-Sieg
Date of first publication:2023/08/02
Copyright:Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
Funding:This work was supported by German Research Foundation grant SFB-TR84, project A6 (W.K.), German Center for Lung Research grant ALI-1.1 (W.K.), German Research Foundation grant SFB-TRR 152, project P10 (F.Z. and T.L.-Z.), German Research Foundation grant SFB 894, project A17 (F.Z. and T.L.-Z.), Research Foundation-Flanders grant FWO/1245321N (B.B.), and German Research Foundation grant SCHU/10-1 (B.S.).
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für funktionale Gen-Analytik (IFGA)
Dewey Decimal Classification (DDC):5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 571 Physiologie und verwandte Themen
Entry in this database:2023/08/11
Licence (German):License LogoCreative Commons - CC BY - Namensnennung 4.0 International