Mouse model of Staphylococcus aureus- and Pseudomonas aeruginosa-induced neutrophilic chronic rhinosinusitis.

Abstract

BACKGROUND: Chronic rhinosinusitis (CRS) is a highly prevalent upper airway disease. Its pathogenesis remains poorly understood, especially non-eosinophilic CRS. Currently, no validated mouse model exists to study disease mechanisms, indicating an important research gap. We aimed at establishing a reproducible mouse model of non-eosinophilic CRS to allow further research on its pathophysiology. METHODOLOGY: Mice were infected with relevant bacteria for sinus disease via surgical insertion of a nasal tampon in their nasal cavity. Inflammatory features in sinus mucosa were evaluated after 4, 8 and 12 weeks on decalcified skulls by histology and immunohistochemistry and by cytospins and enzyme-linked immunoassay on nasal lavage. RESULTS: S. aureus-inoculated mice showed better survival than S. pneumoniae- and P. aeruginosa- inoculated mice. S. aureus and, to lesser extent, P. aeruginosa were still detectable in the nasal lavage up to 12 weeks. Mice with S. aureus and P. aeruginosa-induced CRS showed significant hypertrophia of the epithelium, neutrophilic infiltration and fibrosis in the sinus mucosa, with increased non-Type 2 cytokines in the nasal lavage. CONCLUSIONS: S. aureus and P. aeruginosa are more potent inducers of neutrophilic inflammation than S. pneumoniae in mice. This model allows us to further study non-eosinophilic chronic rhinosinusitis pathophysiology in vivo.