1. Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia.
- Author
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Abdel Wadood N, Hollenhorst MI, Elhawy MI, Zhao N, Englisch C, Evers SB, Sabachvili M, Maxeiner S, Wyatt A, Herr C, Burkhart AK, Krause E, Yildiz D, Beckmann A, Kusumakshi S, Riethmacher D, Bischoff M, Iden S, Becker SL, Canning BJ, Flockerzi V, Gudermann T, Chubanov V, Bals R, Meier C, Boehm U, and Krasteva-Christ G
- Subjects
- Animals, Mice, Interleukin-17 metabolism, Interleukin-17 immunology, Phagocytosis, Pneumonia immunology, Pneumonia microbiology, Pneumonia metabolism, Lung immunology, Connexins metabolism, Mice, Knockout, Female, Male, Tuft Cells, Immunity, Innate, Adenosine Triphosphate metabolism, Adaptive Immunity, Dendritic Cells immunology, Dendritic Cells metabolism, Pseudomonas aeruginosa immunology, Trachea immunology, Mice, Inbred C57BL, Pseudomonas Infections immunology, TRPM Cation Channels metabolism, TRPM Cation Channels immunology
- Abstract
Tracheal tuft cells shape immune responses in the airways. While some of these effects have been attributed to differential release of either acetylcholine, leukotriene C4 and/or interleukin-25 depending on the activating stimuli, tuft cell-dependent mechanisms underlying the recruitment and activation of immune cells are incompletely understood. Here we show that Pseudomonas aeruginosa infection activates mouse tuft cells, which release ATP via pannexin 1 channels. Taste signaling through the Trpm5 channel is essential for bacterial tuft cell activation and ATP release. We demonstrate that activated tuft cells recruit dendritic cells to the trachea and lung. ATP released by tuft cells initiates dendritic cell activation, phagocytosis and migration. Tuft cell stimulation also involves an adaptive immune response through recruitment of IL-17A secreting T helper cells. Collectively, the results provide a molecular framework defining tuft cell dependent regulation of both innate and adaptive immune responses in the airways to combat bacterial infection., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)
- Published
- 2025
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