Tracheal tuft cells release ATP and link innate to adaptive immunity in pneumonia
Abstract
AbstractTracheal 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.
Article Details
Authors (27)
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
Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University
Thomas Gudermann
Vladimir Chubanov
Robert Bals
Carola Meier
Ulrich Boehm
Gabriela Krasteva-Christ