Lack of the hyaluronan receptor CD44 affects the course of bacterial otitis media and reduces leukocyte recruitment to the middle ear

Hyun Woo Lim,Arwa Kurabi,Kwang Pak,Allen F Ryan

doi:10.1186/s12865-019-0302-3

Hyun Woo Lim, Arwa Kurabi + Show 2 more

Open Access

https://doi.org/10.1186/s12865-019-0302-3

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Abstract

BackgroundCD44 is a multifunctional molecule that plays major roles in both leukocyte recruitment and tissue proliferation. Since mucosal hyperplasia and leukocyte infiltration of the middle ear cavity are major features of otitis media, we evaluated the role of CD44 in the pathophysiology and course of this disease in a mouse model of middle ear infection. Expression of genes related to CD44 function were evaluated using gene arrays in wild-type mice. The middle ears of mice deficient in CD44 were inoculated with non-typeable Haemophilus influenzae. Histopathology and bacterial clearance were compared to that seen in wild-type controls.ResultsWe observed strong up-regulation of CD44 and of genes related to its role in leukocyte extravasation into the middle ear, during the course of acute otitis media. Mice deficient in CD44 exhibited reduced early mucosal hyperplasia and leukocyte recruitment, followed by delayed resolution of infection and persistent inflammation.ConclusionsCD44 plays an important role in OM pathogenesis by altering the mucosal growth and neutrophil enlistment. Targeted therapies based on CD44 could be useful adjuncts to the treatment of middle ear infections.

Highlights

CD44 is a multifunctional molecule that plays major roles in both leukocyte recruitment and tissue proliferation
Expression of genes involved in CD44 signaling in WT mice Genes related to CD44 functions were highly regulated during the course of an episode of non-typeable Haemophilus influenzae (NTHi)-induced acute Otitis media (OM)
The leukocyte molecule ITGAM is an integral part of the integrin complex that interacts with vascular ICAM1, and the later upregulation of its gene can be assumed to reflect the capture and entry of leukocytes into the middle ear (ME) which occurs beginning 1 day after ME inoculation with NTHi [12]

Summary

Introduction

CD44 is a multifunctional molecule that plays major roles in both leukocyte recruitment and tissue proliferation. Since mucosal hyperplasia and leukocyte infiltration of the middle ear cavity are major features of otitis media, we evaluated the role of CD44 in the pathophysiology and course of this disease in a mouse model of middle ear infection. The middle ears of mice deficient in CD44 were inoculated with non-typeable Haemophilus influenzae. Otitis media (OM) is the most prevalent bacterial infection in children worldwide. It is the most common reason for antibiotic prescriptions for children in the United States [1]. OM pathogenesis is multifactorial, bacterial infection is a major etiology, leading to mucosal hyperplasia, effusion, and leukocytic infiltration of the middle ear (ME) [3].

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