Highlights d Tracheal chemosensory cells recognize virulence-associated formyl peptides d This activates a TRPM5-dependent pathway, triggering acetylcholine release d Acetylcholine released from chemosensory cells activates mucociliary clearance d Mice with genetic impairment of this pathway are more susceptible to infection

Inflammatory lung diseases are associated with bronchospasm, cough, dyspnea and airway hyperreactivity. The majority of these symptoms cannot be primarily explained by immune cell infiltration. Evidence has been provided that vagal efferent and afferent neurons play a pivotal role in this regard. Their functions can be altered by inflammatory mediators that induce long-lasting changes in vagal nerve activity and gene expression in both peripheral and central neurons, providing new targets for treatment of pulmonary inflammatory diseases.