Sinonasal Innate Immunity

The front line of upper respiratory defense is the sinonasal cavity, which comes into contact with aerosolized particulate debris as well as fungal spores, bacteria, and viruses with every breath. However, in most individuals, the airways remain free of pathological infection, largely due to multiple first-line innate immune mechanisms working in concert to defend the sinonasal epithelium. The primary physical defense is mucociliary transport (MCT), a specialized function of the airway epithelium consisting of two components: mucus production and mucus transport. MCT is complemented by the secretion of antimicrobial peptides (lysozyme, lactoferrin, cathelicidins, and defensins) and reactive oxygen and nitrogen species (hydrogen peroxide and nitric oxide) orchestrated by a multitude of receptors (Toll-like receptors, melanoma differentiation-associated protein 5, retinoic acid-inducible gene 1), T2R38, adrenergic, cholinergic, purinergic, mechanical, and thermal) that directly kill pathogens. Many of these responses are eventually synergistically linked with adaptive immune responses, and alterations or dysregulation of these innate immune pathways may result in varied pathologic states.