Neuroimmune regulation of lung infection and inflammation

Abstract

Abstract The distal airway of the lung is innervated by vagus nerve. Upon stimulation, vagus nerve endings release acetylcholine or neuropeptides via C-fiber afferents to regulate lung infection and immunity. Vagal sensory nerve endings, brain integration center, acetylcholine and α7 nicotinic acetylcholine receptor (nAChR) expressing cells are key components of pulmonary parasympathetic inflammatory reflex. Meanwhile, this local machinery synergizes with spleen (as a functional hub of cholinergic anti-inflammatory pathway) to finely tune recruitment of the splenic α7 nAChR+CD11b+ cells into the inflamed lungs during lung infection. Recent studies have showed that lung group 2 innate lymphoid cells (ILC2) express both α7 nAChR and neuropeptide receptors. Acetylcholine and neuropeptides can regulate ILC2 and reshape pulmonary infection and immunity. Among the airway epithelial cells, pulmonary neuroendocrine cells are rare cell population; however, these cells are innervated by sensory nerve endings and they could secrete neuropeptides that influence lung infection and immunity.