Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia
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.
Authors
- Stephan Maxeiner (ORCID: https://orcid.org/0000-0002-4472-695X)
- Mohamed Ibrahem Elhawy (ORCID: https://orcid.org/0000-0002-8252-1832)
- Sandra Iden (ORCID: https://orcid.org/0000-0003-2333-9827)
- Amanda Wyatt (ORCID: https://orcid.org/0000-0003-1107-3857)
- Monika I. Hollenhorst (ORCID: https://orcid.org/0000-0002-2690-4388)
- C. Englisch
- Markus Bischoff (ORCID: https://orcid.org/0000-0001-6734-2732)
- Ulrich Boehm (ORCID: https://orcid.org/0000-0003-2436-6907)
- Robert Bals (ORCID: https://orcid.org/0000-0002-1472-9535)
- Brendan J. Canning (ORCID: https://orcid.org/0000-0003-4197-5560)
- Noran Abdel Wadood (ORCID: https://orcid.org/0000-0001-6108-1797)
- Veit Flockerzi (ORCID: https://orcid.org/0000-0001-6002-6294)
- Elmar Krause (ORCID: https://orcid.org/0000-0003-0891-2373)
- Carola Meier (ORCID: https://orcid.org/0000-0002-3839-8080)
- Dieter Riethmacher (ORCID: https://orcid.org/0000-0002-4206-5529)
- Thomas Gudermann (ORCID: https://orcid.org/0000-0002-0323-7965)
- Christian Herr (ORCID: https://orcid.org/0000-0001-9422-6569)
- Sören L. Becker (ORCID: https://orcid.org/0000-0003-3634-8802)
- Daniela Yildiz (ORCID: https://orcid.org/0000-0002-9702-8581)
- Na Zhao (ORCID: https://orcid.org/0000-0003-1780-7700)
- Ann-Kathrin Burkhart (ORCID: https://orcid.org/0000-0003-4128-6677)
- Saskia B. Evers
- Gabriela Krasteva‐Christ (ORCID: https://orcid.org/0000-0002-0113-521X)
- Vladimir Chubanov (ORCID: https://orcid.org/0000-0002-6042-4193)
- Soumya Kusumakshi
- Anja Beckmann
- Mahana Sabachvili (ORCID: https://orcid.org/0009-0000-9480-834X)
Institutions
- Helmholtz Centre for Infection Research (DE)
- German Center for Lung Research (DE)
- Institute of Medical Microbiology and Hygiene (DE)
- Helmholtz Institute for Pharmaceutical Research Saarland (DE)
- Nazarbayev University (KZ)
- Ludwig-Maximilians-Universität München (DE)
- Saarland University (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-01-10
- DOI
- https://doi.org/10.1038/s41467-025-55936-5
- Citations
- 15
- Primary Topic
- Biochemical Analysis and Sensing Techniques
- Type
- article
- Field-Weighted Citation Impact
- 16.79
Funders
- Deutsche Forschungsgemeinschaft
- Universität des Saarlandes
- Ludwig-Maximilians-Universität München
- National Institutes of Health