Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia

Noran Abdel Wadood; Monika I. Hollenhorst; Mohamed Ibrahem Elhawy; Na Zhao; Clara Englisch; Saskia B. Evers; Mahana Sabachvili; Stephan Maxeiner; Amanda Wyatt; Christian Herr; Ann Kathrin Burkhart; Elmar Krause; Daniela Yildiz; Anja Beckmann; Soumya Kusumakshi; Dieter Riethmacher; Markus Bischoff; Sandra Iden; Sören L. Becker; Brendan J. Canning; Veit Flockerzi; Thomas Gudermann; Vladimir Chubanov; Robert Bals; Carola Meier; Ulrich Boehm; Gabriela Krasteva-Christ

doi:10.1038/s41467-025-55936-5

Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia

Noran Abdel Wadood, Monika I. Hollenhorst, Mohamed Ibrahem Elhawy, Na Zhao, Clara Englisch, Saskia B. Evers, Mahana Sabachvili, Stephan Maxeiner, Amanda Wyatt, Christian Herr, Ann Kathrin Burkhart, Elmar Krause, Daniela Yildiz, Anja Beckmann, Soumya Kusumakshi, Dieter Riethmacher, Markus Bischoff, Sandra Iden, Sören L. Becker, Brendan J. CanningVeit Flockerzi, Thomas Gudermann, Vladimir Chubanov, Robert Bals, Carola Meier, Ulrich Boehm, Gabriela Krasteva-Christ

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

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.

Original language	English
Article number	584
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-55936-5
Publication status	Published - Dec 2025
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Abdel Wadood, N., Hollenhorst, M. I., Elhawy, M. I., Zhao, N., Englisch, C., Evers, S. B., Sabachvili, M., Maxeiner, S., Wyatt, A., Herr, C., Burkhart, A. K., Krause, E., Yildiz, D., Beckmann, A., Kusumakshi, S., Riethmacher, D., Bischoff, M., Iden, S., Becker, S. L., ... Krasteva-Christ, G. (2025). Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia. Nature Communications, 16(1), Article 584. https://doi.org/10.1038/s41467-025-55936-5

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 & Krasteva-Christ, G 2025, 'Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia', Nature Communications, vol. 16, no. 1, 584. https://doi.org/10.1038/s41467-025-55936-5

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title = "Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia",

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.",

author = "\{Abdel Wadood\}, Noran and Hollenhorst, \{Monika I.\} and Elhawy, \{Mohamed Ibrahem\} and Na Zhao and Clara Englisch and Evers, \{Saskia B.\} and Mahana Sabachvili and Stephan Maxeiner and Amanda Wyatt and Christian Herr and Burkhart, \{Ann Kathrin\} and Elmar Krause and Daniela Yildiz and Anja Beckmann and Soumya Kusumakshi and Dieter Riethmacher and Markus Bischoff and Sandra Iden and Becker, \{S{\"o}ren L.\} and Canning, \{Brendan J.\} and Veit Flockerzi and Thomas Gudermann and Vladimir Chubanov and Robert Bals and Carola Meier and Ulrich Boehm and Gabriela Krasteva-Christ",

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AU - Abdel Wadood, Noran

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AU - Elhawy, Mohamed Ibrahem

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AU - Englisch, Clara

AU - Evers, Saskia B.

AU - Sabachvili, Mahana

AU - Maxeiner, Stephan

AU - Wyatt, Amanda

AU - Herr, Christian

AU - Burkhart, Ann Kathrin

AU - Krause, Elmar

AU - Yildiz, Daniela

AU - Beckmann, Anja

AU - Kusumakshi, Soumya

AU - Riethmacher, Dieter

AU - Bischoff, Markus

AU - Iden, Sandra

AU - Becker, Sören L.

AU - Canning, Brendan J.

AU - Flockerzi, Veit

AU - Gudermann, Thomas

AU - Chubanov, Vladimir

AU - Bals, Robert

AU - Meier, Carola

AU - Boehm, Ulrich

AU - Krasteva-Christ, Gabriela

PY - 2025/12

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Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia

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