Mechanistic modelling of upper airway immune dysfunction in children with otitis media with effusion

Otitis media with effusion (OME) is an inflammatory condition of the middle ear which affects >80% of children by 10 years of age. It is a leading cause of hearing loss and developmental delay. The nasopharyngeal lymphoid tissue or ‘adenoid’ is closely associated with the middle ear via the eustachian tube. Utilising single-cell RNA sequency technology I previous demonstrated, for the first time, that children with OME have disordered B cell maturation in their adenoids, likely hampering effective adaptive immune responses to nasopharyngeal stimuli. However, the mechanism behind this remains unknown. During my postdoctoral time I have developed a novel in vitro model of the paediatric adenoid which is amenable to infective challenge. I propose to extend this work by characterising B cell responses in this model, derived from OME and control adenoid biopsies. Objectives: 1) Extend my training in mucosal immunology, laying the foundation for future fellowship applications seeking to understand the mechanisms of middle ear inflammatory disease. 2) Identify localised immune dysfunction and mechanisms associated with OME pathogenesis worthy of further exploration, with the ultimate aim of developing novel intranasal therapies. I hypothesise that OME pathogenesis is driven by a localised deficiency of adenoidal B cell pathogen response due to defective T cell help provided to B cells in the germinal centre, leading to impaired mature memory and plasma cell formation.