Loss of the homeostatic protein BPIFA1, leads to exacerbation of otitis media severity in the Junbo mouse model

Apoorva Mulay,Debbie Williams,Derek W Hood,Colin D Bingle,Michael Cheeseman,Catherine Russell,Lynne Bingle,Steve D M Brown

doi:10.1038/s41598-018-21166-7

Apoorva Mulay, Debbie Williams + Show 6 more

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https://doi.org/10.1038/s41598-018-21166-7

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Abstract

Otitis Media (OM) is characterized by epithelial abnormalities and defects in innate immunity in the middle ear (ME). Although, BPIFA1, a member of the BPI fold containing family of putative innate defence proteins is abundantly expressed by the ME epithelium and SNPs in Bpifa1 have been associated with OM susceptibility, its role in the ME is not well characterized. We investigated the role of BPIFA1 in protection of the ME and the development of OM using murine models. Loss of Bpifa1 did not lead to OM development. However, deletion of Bpifa1 in Evi1Jbo/+ mice, a model of chronic OM, caused significant exacerbation of OM severity, thickening of the ME mucosa and increased collagen deposition, without a significant increase in pro-inflammatory gene expression. Our data suggests that BPIFA1 is involved in maintaining homeostasis within the ME under steady state conditions and its loss in the presence of inflammation, exacerbates epithelial remodelling leading to more severe OM.

Highlights

Otitis Media (OM), or middle ear (ME) inflammation, is the most prevalent paediatric disease and the leading cause of paediatric surgery, antibiotic prescription and conductive hearing impairment[1]
BPIFA1 was detected in the non-ciliated epithelium enclosing this mesenchyme mass, in the region where it retracted from the opposing epithelial surface (Fig. 1A,B)
The epithelium that lines the internal surface of the tympanic membrane (Tm) stained positively for BPIFA1 (Fig. 1F)

Summary

Introduction

Otitis Media (OM), or middle ear (ME) inflammation, is the most prevalent paediatric disease and the leading cause of paediatric surgery, antibiotic prescription and conductive hearing impairment[1]. We recently showed production of BPIFA1 in the murine ME, in vivo and in vitro[29] and it has been reported that Bpifa1−/− mice greater than 10 months-of-age show increased susceptibility to spontaneous development of chronic OM30. Together this data suggests that BPIFA1 may be a determinant for predisposition to OM. Our data suggests that BPIFA1 is involved in maintaining homeostasis within the ME under steady state conditions This is the first study to report the use of compound Bpifa[1] mutants and it underlines the importance of investigating the additive effect of multiple genetic defects in order to better understand the aetiology of multifactorial diseases such as OM

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