Staphylococcus aureus is capable of inducing a neutrophilic inflammation in a surgical mouse model of CRS, in a more prominent way than Pseudomonas aeruginosa or Streptococcus pneumoniae - 17/02/23

Chronic rhinosinusitis (CRS) is an inflammatory respiratory disease with symptoms of nasal blockade, headache, loss of smell and nasal secretions that last for at least 12weeks. It affects 11% of European population and is a global health burden, affecting the quality of life of patients and being responsible for high health-care costs. CRS is classified according to inflammatory profile as type 2 eosinophilic, associated to CRS with nasal polyps in the western world, or non-type 2 neutrophilic CRS, associated to CRS without nasal polyps in the western world [1Bachert C., Marple B., Schlosser R.J., Hopkins C., Schleimer R.P., Lambrecht B.N., et al. Adult chronic rhinosinusitis Nat Rev Dis Primers 2020 ;  6 : 86

Cliquez ici pour aller à la section Références]. Currently, the pathogenesis of CRS is not fully understood. Compared to type 2 CRS, there is a huge gap concerning non-type 2 CRS, for which no validated mouse model is available to study disease mechanisms. Jacob et al. described a mouse model of non-T2 CRS based on a surgical introduction of an infected nasal tampon [2Jacob A., Faddis B.T., Chole R.A. Chronic bacterial rhinosinusitis: description of a mouse model Arch Otolaryngol Head Neck Surg 2001 ;  127 : 657-664 [cross-ref]

Cliquez ici pour aller à la section Références]. In order to explore pathophysiological mechanisms of non-type 2 CRS, we aimed at establishing a neutrophilic mouse model of bacterial-induced CRS.

A nasal tampon was micro-surgically inserted in the nasal cavity of 72 mice and was then inoculated with 10μL of 10⁷ CFU/mL solution of three different bacteria relevant to sinus disease: Staphylococcus aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa (A). In a pilot experiment, we confirmed the presence of the nasal tampon inoculated with saline solution does not induce any inflammation or alter maxillary sinuses epithelial integrity (B). Inflammatory features in the nasal mucosa were evaluated after 4, 8 and 12weeks on decalcified skulls by histology and immunohistochemistry. Antibodies were measured in nasal lavage (NL) by ELISA. Differential cell-counts and cytokines measurements were performed in NL and broncho-alveolar lavage (BAL). Kruskal–Wallis test was applied for statistical analysis (*P<0.05; **P<0.01).

Postoperative mortality was observed to be more important for S. pneumoniae and P. aeruginosa than for S. aureus (C). While S. aureus and P. aeruginosa were still detectable in the nasal lavage after 4, 8 and 12weeks post-surgery, S. pneumoniae seemed to be cleared easier (D). Mice with S. aureus-induced experimental CRS showed a significant increase in the epithelial thickness (4, 8, 12 w), subepithelial fibrosis (12 w), and neutrophilic infiltration (4, 8 w) in the nasal mucosa (E) that was also confirmed in the NL (F). Mice with P. aeruginosa-induced experimental CRS showed significantly increased epithelial thickness (12 w) and subepithelial fibrosis (12 w) (E). Mice with S. pneumoniae-induced experimental CRS did not show any significant inflammatory changes at any timepoint (E) (Fig. 1).

S. aureus is the most potent inducer of neutrophilic non-type 2 CRS in a mouse model of bacterial-induced CRS. This mouse model allows us to further investigate the pathogenesis of non-type 2 CRS.