Project Details
Projekt
Tuft cell-neuronal communication in the respiratory system
Applicant
Professorin Dr. Gabriela Krasteva-Christ
Subject Area
Cell Biology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 564826411
The airway epithelium is frequently exposed to pathogens, allergens, and pollutants, serving as the first line of defense in the respiratory tract. Recent studies, including our own, have shown that specialized solitary chemosensory epithelial cells formally known as brush cells and now as tuft cells, play a key role in detecting the presence of bacteria and parasites. Previously, we have demonstrated that airway tuft cells are closely associated with sensory nerve fibers, suggesting a tight functional interaction between these cell types. Activation of tuft cells mediates protective responses such as increased mucociliary clearance, changes in respiratory rate or induction of a protective neurogenic inflammation, leading to improved survival in pneumonia. Nevertheless, the secreted molecules essential for communicating these sensory signals to the brain and immune system, and the resulting feedback to peripheral tissues, remain largely elusive. Tuft cells synthesize and release upon activation, e.g, by bacterial metabolites, the neurotransmitter acetylcholine (ACh), cytokines, and cysteinyl leukotrienes that may influence both neuronal activity and immune cell function. Consequently, the emerging role of tuft cell-neuronal interactions in priming the environment warrants thorough investigation. In this study, we aim to explore how tuft cells interact with sensory neurons. Our objectives are to understand how this crosstalk contributes to 1) changes in the tuft cell population and function, 2) alterations in neuronal sensitivity, and 3) host defense mechanisms. We will employ genetic mouse models, transcriptomic analyses, tuft cell-neuronal co-cultures, electrophysiology and electron microscopy to characterize the contacts and identify key molecules and mechanisms driving the communication between tuft cells and neurons, and immune cells. In addition, we will utilize in vivo imaging and optogenetic techniques to evaluate the relationship between airway tuft cells and sensory neurons in vitro and ex vivo. We anticipate identifying the signals, signaling molecules, and mechanisms involved in reciprocal communication through cell-cell interactions, ultimately enhancing our understanding of the interdependence among rare cell types in the epithelial layer such as tuft cells and neurons of both healthy and challenged airways and lungs (e.g., in bacterial pneumonia).
DFG Programme
Priority Programmes
