A murine sinonasal infection model recapitulates key features of clinical chronic rhinosinusitis

Introduction. Chronic rhinosinusitis is a difficult-to-treat, recurrent inflammatory condition of the nose and paranasal sinuses with global prevalence. Despite its impact on patient quality of life and its cost to the healthcare system, the pathogenesis of chronic rhinosinusitis (CRS) remains poorly understood. Additionally, while the presence of bacteria in CRS has been confirmed by numerous studies, their influence on disease symptoms is unclear. Disease-relevant models can help resolve these questions.Hypothesis. We hypothesized that bacterial inoculation could drive CRS-associated symptoms in a murine model.Aim. To characterize host-microbe interactions in a murine model of sinonasal bacterial infection.Methodology. Staphylococcus aureus and/or Pseudomonas aeruginosa were inoculated in the nasal cavity of Swiss Webster, C57Bl/6, Balb/c and B6.Cg-Prkdc ^scid/SzJ severe combined immunodeficient (SCID) mice. Systemic cytokine response was quantified with a multiplexed enzyme-linked immunosorbent assay, and local histological alterations were quantified using haematoxylin and eosin as well as Alcian Blue-Periodic Acid-Schiff-stained sinonasal sections.Results. Intranasal bacterial inoculation induced symptoms of CRS in murine sinonasal cavities. Dual species inoculation generated a unique response compared to single species. Repeated inoculations did not result in bacterial clearance from immunological priming. While Swiss Webster and C57Bl/6 mice demonstrated the greatest magnitude of responses, Balb/c mice demonstrated a protective response, generally downregulating cytokines and attempting to prevent further tissue damage. SCID mice demonstrated effective clearance of P. aeruginosa by innate immunity, but maintenance of S. aureus.Conclusion. Pathogenic bacteria are able to persist and drive the development of symptoms associated with clinical CRS in a murine model. Bacterial interactions and host factors influence CRS-associated inflammation. By investigating host responses from a number of mouse genetic backgrounds, the heterogeneity of disease presentation in CRS can be modelled, and strategies for infection management can be evaluated as potential therapeutic targets.