Innate Immunity in the Middle Ear Mucosa

Abstract

Otitis media (OM) encompasses a spectrum of clinical presentations ranging from the readily identifiable Acute OM (AOM), which is characterised by otalgia and fever, to chronic otitis media with effusion (COME) where impaired hearing due to middle ear effusion may be the only clinical symptom. Chronic suppurative OM (CSOM) presents as a more severe form of OM, involving perforation of the tympanic membrane. The pathogenesis of OM in these varied clinical presentations is unclear but activation of the innate inflammatory responses to viral and/or bacterial infection of the upper respiratory tract performs an integral role. This localised inflammatory response can persist even after pathogens are cleared from the middle ear, eustachian tubes and, in the case of respiratory viruses, even the nasal compartment. Children prone to OM may experience an over exuberant inflammatory response that underlies the development of chronic forms of OM and their sequelae, including hearing impairment. Treatments for chronic effusive forms of OM are limited, with current therapeutic guidelines recommending a “watch and wait” strategy rather than active treatment with antibiotics, corticosteroids or other anti-inflammatory drugs. Overall, there is a clear need for more targeted and effective treatments that either prevent or reduce the hyper-inflammatory response associated with chronic forms of OM. Improved treatment options rely upon an in-depth understanding of OM pathogenesis, particularly the role of the host innate immune response during acute OM. In this paper, we review the current literature regarding the innate immune response within the middle ear to bacterial and viral otopathogens alone, and as co-infections. This is an important consideration, as the role of respiratory viruses as primary pathogens in OM is not yet fully understood. Furthermore, increased reporting from PCR-based diagnostics, indicates that viral/bacterial co-infections in the middle ear are more common than bacterial infections alone. Increasingly, the mechanisms by which viral/bacterial co-infections may drive or maintain complex innate immune responses and inflammation during OM as a chronic response require investigation. Improved understanding of the pathogenesis of chronic OM, including host innate immune response within the middle ear is vital for development of improved diagnostic and treatment options for our children.

Immunomodulation as a Protective Strategy in Chronic Otitis Media

“…In addition to pathogenesis, innate immunity plays a significant role in OM resolution ( Massa et al., 2021 ). In the normal child, OM typically recovers within a few days, too soon for adaptive immunity to be engaged ( Leichtle et al., 2011 ).…”

Resolution of otitis media in a humanized mouse model

“…The cost for producing these mice and purchasing them is still high (∼$400 to $1,200 per mouse) for a conventional laboratory model. Finally, induction of OM by direct inoculation of a single bacterium into the ME is rather not similar to clinical human disease where the pathogenesis involved nasopharyngeal colonization followed by ascent to the ME and polymicrobial infection ( Bakaletz, 2010 ; Massa et al, 2021 ). It has been shown that the host responses vary by pathogen species [e.g., ( Melhus and Ryan, 2000 ; Liu et al, 2013 )].…”

Otitis media: recent advances in otitis media vaccine development and model systems

“…The ME mucosa, like other mucosal surfaces in the body, has a local immune system that plays a critical role in protecting against infections. The ME mucosa and URT are connected anatomically, and their immune systems are interconnected as well ( Massa et al, 2021 ; Kurono, 2022 ). To prevent OM, enhancement of mucosal immune responses in the nasopharynx (NP) and ME is desired, however, how the immune protection in the ME mucosa relates to URT is still poorly understood.…”