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 an...
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Nature Portfolio
2025-01-01
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Online Access: | https://doi.org/10.1038/s41467-025-55936-5 |
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author | 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 |
author_facet | 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 |
author_sort | Noran Abdel Wadood |
collection | DOAJ |
description | 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. |
format | Article |
id | doaj-art-4274aecf6f794e35955ef0fd219345a4 |
institution | Kabale University |
issn | 2041-1723 |
language | English |
publishDate | 2025-01-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Nature Communications |
spelling | doaj-art-4274aecf6f794e35955ef0fd219345a42025-01-12T12:29:59ZengNature PortfolioNature Communications2041-17232025-01-0116111710.1038/s41467-025-55936-5Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumoniaNoran Abdel Wadood0Monika I. Hollenhorst1Mohamed Ibrahem Elhawy2Na Zhao3Clara Englisch4Saskia B. Evers5Mahana Sabachvili6Stephan Maxeiner7Amanda Wyatt8Christian Herr9Ann-Kathrin Burkhart10Elmar Krause11Daniela Yildiz12Anja Beckmann13Soumya Kusumakshi14Dieter Riethmacher15Markus Bischoff16Sandra Iden17Sören L. Becker18Brendan J. Canning19Veit Flockerzi20Thomas Gudermann21Vladimir Chubanov22Robert Bals23Carola Meier24Ulrich Boehm25Gabriela Krasteva-Christ26Institute of Anatomy and Cell Biology, Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityExperimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland UniversityDepartment of Internal Medicine V-Pulmonology, Allergology, Intensive Care Medicine, Saarland University HospitalInstitute of Anatomy and Cell Biology, Saarland UniversityDepartment of Cellular Neurophysiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), Saarland UniversityCenter for Gender-Specific Biology and Medicine (CGBM), Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityExperimental Pharmacology, Center for Molecular Signaling (PZMS), Saarland UniversityDepartment of Biomedical Sciences, School of Medicine, Nazarbayev UniversityInstitute for Medical Microbiology and Hygiene, Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityInstitute for Medical Microbiology and Hygiene, Saarland UniversityThe Johns Hopkins Asthma and Allergy CenterInstitute for Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityWalther-Straub Institute of Pharmacology and Toxicology, LMU MunichWalther-Straub Institute of Pharmacology and Toxicology, LMU MunichCenter for Gender-Specific Biology and Medicine (CGBM), Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityCenter for Gender-Specific Biology and Medicine (CGBM), Saarland UniversityInstitute of Anatomy and Cell Biology, Saarland UniversityAbstract 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.https://doi.org/10.1038/s41467-025-55936-5 |
spellingShingle | 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 Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia Nature Communications |
title | Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia |
title_full | Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia |
title_fullStr | Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia |
title_full_unstemmed | Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia |
title_short | Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia |
title_sort | tracheal tuft cells release atp and link innate to adaptive immunity in pneumonia |
url | https://doi.org/10.1038/s41467-025-55936-5 |
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