Establishment of a mouse model of bacterial induced non-type 2 Chronic Rhinosinusitis

Details

Supervisors

Hox, Valérie

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité spécialisée: toxicologie

Abstract

Rhinosinusitis is one of the most frequent human diseases with a prevalence between 5% and 11% in Europe. Its chronic form is known as Chronic Rhinosinusitis (CRS) and is defined as an inflammation of the mucosa of the nose and paranasal sinuses for at least 12 weeks. The symptoms include hyposmia, nasal obstruction, nasal discharge, and facial pain. CRS can be differentiated into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). The relative prevalence of these CRS phenotypes in the western population are approximately around 80% for CRSsNP and 20% for CRSwNP. These phenotypes differ by their clinical appearances, their histopathological features and by their inflammatory profile. Inflammatory responses can be divided into type-2 (T2) and non-T2 profiles. The T2 subtype leads to a production of Th2 linked cytokines (Interleukin -4 and -13) that results in an eosinophilic infiltration and is often linked to the presence of nasal polyps (CRSwNP). While the non-T2 is associated to the production of Th1/Th17 cytokines leading to a neutrophilic infiltration which rarely comes with polyp formation (CRSsNP). Most of the research performed on CRS is focusing on T2 inflammatory CRSwNP disease and there is an important lack of studies investigating the non-T2 CRSsNP phenotype. The principal objective of this master thesis was to establish a relevant mouse model of non-type 2 CRS, based on a surgical introduction of an infected nasal tampon with the intention, in the future, of exploring the role of IgA and its polymeric Immunoglobulin receptor (pIgR) in the development of CRS in vivo. To achieve this purpose, we have optimized the technique and carried out surgeries on mice with conditions involving the following bacteria: Staphylococcus aureus, Streptcoccus Pneumoniae and Pseudomonas aeruginosa. This study has shown that the model does work, however, not for all conditions. S. pneumoniae showed no significant outcomes in favor of inflammation. On the other hand, S. aureus and P. aeruginosa were able to be cultured from mice at all timepoints and these strains showed major neutrophilic recruitment and histopathological features related to CRS, with significant statistical differences for S. aureus compared to controls.