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

ABSTRACT: 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 cil

SUBMITTER: Perniss A 

PROVIDER: S-EPMC10396310 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature