Perniss, AlexanderAlexanderPernissBoonen, BrettBrettBoonenTonack, SarahSarahTonackThiel, MoritzMoritzThielPoharkar, KrupaliKrupaliPoharkarAlnouri, Mohamad WessamMohamad WessamAlnouriKeshavarz, MaryamMaryamKeshavarzPapadakis, TamaraTamaraPapadakisWiegand, SilkeSilkeWiegandPfeil, UweUwePfeilRichter, KatrinKatrinRichterAlthaus, MikeMikeAlthausOberwinkler, JohannesJohannesOberwinklerSchütz, BurkhardBurkhardSchützBoehm, UlrichUlrichBoehmOffermanns, StefanStefanOffermannsLeinders-Zufall, TreseTreseLeinders-ZufallZufall, FrankFrankZufallKummer, WolfgangWolfgangKummer2024-02-082024-02-082023https://jlupub.ub.uni-giessen.de/handle/jlupub/19006http://dx.doi.org/10.22029/jlupub-18367Host-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.enNamensnennung 4.0 Internationalddc:570