A novel bacterial-derived peptide involved in patho-sensing in the nasal mucosa: the function of the chemosensory epithelial cellneuronal circuit.

The nose is a functionally sophisticated component of the respiratory system. It also is the point of first entry of inhaled air. Inside the nasal passages, a sophisticated epithelium lines the mucosal surface. Below the mucosal surface sensory nerve endings traverse the mucosa and provide a broad sensitivity for temperature, chemosensory cues and pathogens. In addition to innervating the sub-epithelial lumen, sensory nerve endings protrude into the epithelial layer and make functional contacts with specialized epithelial chemosensory cells (CSCs) exposed to the nasal lumen. CSCs are remarkable cells, with unique pathways, for instance the taste-like transduction pathway. Upon activation, CSCs trigger neurons prompting protective responses such as local inflammation, increased mucociliary clearance and reduced breathing rate. Recent studies have underscored the importance of these CSCs as inflammatory regulators with an emerging role in pathosensing. Recently a novel family of bacteria-derived peptides was described as virulence-associated signals. We have now discovered that members of this family activate CSCs and trigger innate defense mechanisms. We will now extensively investigate the signal transduction pathways at the basis of this activation. Then we will focus on the activation of the neuronal compartment of the ciruit, by using this peptide-activation as the basis for identifying CSCinnervated neurons.