Noran Abdel Wadood, Monika I. Hollenhorst und Mohamed Ibrahem Elhawy (equally contributing first authors)from the research lab of Prof. Gabriela Krasteva-Christ, Institute of Anatomy und Cell Biology at the Saarland University, Homburg as well as their co-authors have been awarded the Quarterly Publication Award (QPA) I/2025 of the Anatomische Gesellschaft for their study Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia recently published in Nature Communications.
Tuft cells are rare chemosensory epithelial cells that serve as sentinels at mucosal surfaces. In this study we demonstrate a novel role for tracheal tuft cells in modulating immune responses during pulmonary bacterial infection. We show that tuft cells release ATP in Trpm5-dependent manner via the pannexin-1 channel upon stimulation with the bitter tasting compound denatonium or during infectionwith P. aeruginosa. Tuft cell-released ATP promotes dendritic cell recruitment and activation and enhances the phagocytic capacity in murine tracheae and lungs leading to increased survival rates in pneumonia. Notably, tuft cell-derived ATP also influences adaptive immunity by increasing pulmonary TH17 cell recruitment and plasma levels of IL-17A. Our study provides the first strong evidence that tuft cell-derived ATP induces protective immune responses that bridge innate and adaptive immunity and are crucial for combating bacterial infections.
Tracheal tuft cells release ATP upon stimulation and induce protective immune responses which bridge the innate and adaptive immunity and are crucial for combating bacterial infections. A) Representative current-voltage (I-V) relationships of whole-cell currents measured in a tracheal tuft cell from a Trpm5+/+ or a Trpm5−/− mouse in the presence of 1 µM intracellular Ca2+. B) ATP levels in supernatants from denatonium- and vehicle-treated tracheae of Trpm5+/+ mice and Trpm5−/− mice. C) Representative immunofluorescence staining of tuft cells (Trpm5-positive, arrows) and dendritic cells (CD11c-positive, arrow heads) in tracheal cross sections from naïve and CNO-stimulated mice. D) Percentage of activated dendritic cells (CD86+ DCs) in tracheae three days post infection or in uninfected controls in Trpm5+/+, Trpm5-/- and Panx1-/- mice. E) Graphical summary. Stimulation of tuft cells (with denatonium or CNO in Trpm5-DREADD mouse model) activates Trpm5, resulting in ATP release via pannexin-1 and tuft cell expansion. The released ATP drives DC recruitment, migration, activation, and phagocytosis, promotes TH17 cell recruitment and IL-17A secretion.
