β2-adrenergic signaling promotes anti-inflammatory response and viral clearance during neonatal respiratory syncytial virus infection 3031

Description Respiratory syncytial virus (RSV) is the leading cause of acute bronchiolitis and pneumonia in children globally. RSV infection is characterized by mild symptoms like wheezing, coughing, and sneezing caused by lung inflammation, and viral amplification. The crosstalk between neurons and immune and non-immune cells develops from early life onwards. The lungs and airways are densely innervated by sympathetic neurons that secrete the neurotransmitter noradrenaline (NA) at homeostasis and following injury in adult mice. However, it is unknown whether sympathetic neurons regulate anti-viral immunity in neonates and early-life infections. NA, once secreted into the lungs, can act on immune and non-immune cells through β-adrenergic receptors (β-ARs). In a mouse model of neonatal RSV infection, we find that the stimulation of adrenergic signaling via the β2-AR agonist (Albuterol) robustly increases viral clearance, anti-inflammatory responses, and disease recovery. By contrast, the loss of sympathetic neurons and the β2-AR increases the RSV load in neonatal mice. β2-AR signaling had the downstream effect of reduced airway mucus secretion which prevented respiratory failure, airway blockade, and facilitated control of RSV infection. Collectively, our study shows that sympathetic neurons and β2-AR signaling protect neonates from viral expansion and inflammation to promote antiviral defense. Funding Sources Supported by National Institutes of Health (NIH) R35GM155117 and P20GM113117, American Lung Association (COVID-19 & Respiratory Virus Research Award), American Heart Association (Transformational Project Award), and Kansas State University Johnson Cancer Research Center (JCRC)