The role of TNF-α and IL-1β in virus-induced M2 receptor dysfunction

Respiratory viral infections trigger most asthma exacerbations by disrupting neural airway control. Normally, M2 muscarinic receptors on parasympathetic neurons inhibit acetylcholine release, but infection induces M2 dysfunction, causing bronchoconstriction. Using mouse and guinea pig models, I showed influenza and parainfluenza viruses infect airway epithelium, not neurons, implicating inflammatory mediators. I developed a novel dissection technique and demonstrated that parainfluenza infection decreases neuronal M2 receptor expression via TNF-α and IL-1β. Blocking IL-1β preserved M2 function and prevented airway hyperreactivity. These findings identify IL-1β as a key mediator and suggest IL-1β inhibition as a potential therapy for virus-induced asthma exacerbations.