Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia
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. Canning B.J. Flockerzi V. Gudermann T. Chubanov V. Bals R. Meier C. Boehm U. Krasteva-Christ G.
December 2025Nature Research
Nature Communications
2025#16Issue 1
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.
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Institute of Anatomy and Cell Biology, Saarland University, Homburg, Germany
Center for Gender-Specific Biology and Medicine (CGBM), Saarland University, Homburg, Germany
Experimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany
Department of Internal Medicine V-Pulmonology, Allergology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany
Cell and Developmental Biology, Center of Human and Molecular Biology (ZHMB), Saarland University, Faculty of Medicine, Homburg, Germany
Department of Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland University, Homburg, Germany
Institute for Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland University, Homburg, Germany
Department of Biomedical Sciences, School of Medicine, Nazarbayev University, Astana, Kazakhstan
Institute for Medical Microbiology and Hygiene, Saarland University, Homburg, Germany
The Johns Hopkins Asthma and Allergy Center, Baltimore, MD, United States
Walther-Straub Institute of Pharmacology and Toxicology, LMU Munich, Munich, Germany
Comprehensive Pneumology Center, a member of the German Center for Lung Research (DZL), Munich, Germany
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarbrücken, Germany
Institute of Anatomy and Cell Biology
Center for Gender-Specific Biology and Medicine (CGBM)
Experimental Pharmacology
Department of Internal Medicine V-Pulmonology
Cell and Developmental Biology
Department of Cellular Neurophysiology
Institute for Experimental and Clinical Pharmacology and Toxicology
Department of Biomedical Sciences
Institute for Medical Microbiology and Hygiene
The Johns Hopkins Asthma and Allergy Center
Walther-Straub Institute of Pharmacology and Toxicology
Comprehensive Pneumology Center
Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)
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