Exosome swarms eliminate airway pathogens and provide passive epithelial immunoprotection through nitric oxide

摘要: Background Nasal mucosa–derived exosomes (NMDEs) harbor immunodefensive proteins and are capable of rapid interepithelial protein transfer. Objectives We sought to determine whether mucosal exposure inhaled pathogens stimulates a defensive swarm microbiocidal exosomes, which also donate their antimicrobial cargo adjacent epithelial cells. Methods performed an institutional review board–approved study healthy NMDE secretion after Toll-like receptor (TLR) 4 stimulation by LPS (12.5 μg/mL) in the presence TLR4 inhibitors. Interepithelial transfer exosomal nitric oxide (NO) synthase was measured using ELISAs NO activity assays. Exosomal assays were with Pseudomonas aeruginosa. Proteomic analyses SOMAscan. Results In vivo in vitro induced 2-fold increase along inducible expression function through inhibitor nuclear factor κB kinase activation. increased against P aeruginosa almost 2 orders magnitude. LPS-stimulated 4-fold production within autologous cells 5 minutes contact. Pathway analysis proteome revealed 44 additional associated signaling innate immune function. Conclusions provide direct in vivo evidence for novel exosome-mediated immunosurveillance defense mechanism human upper airway. These findings have implications lower airway immunity, delivery therapeutics, host microbiome regulation.