Abstract
Acute otitis media (AOM) is commonly caused by bacterial pathobionts of the nasopharynx that ascend the Eustachian tube to cause disease in the middle ears. To model and study the various complexities of AOM, common human otopathogens are injected directly into the middle ear bullae of rodents or are delivered with viral co-infections which contribute to the access to the middle ears in complex and partially understood ways. Here, we present the novel observation that Bordetella bronchiseptica, a well-characterized respiratory commensal/pathogen of mice, also efficiently ascends their Eustachian tubes to colonize their middle ears, providing a flexible mouse model to study naturally occurring AOM. Mice lacking T and/or B cells failed to resolve infections, highlighting the cooperative role of both in clearing middle ear infection. Adoptively transferred antibodies provided complete protection to the lungs but only partially protected the middle ears, highlighting the differences between respiratory and otoimmunology. We present this as a novel experimental system that can capitalize on the strengths of the mouse model to dissect the molecular mechanisms involved in the generation and function of immunity within the middle ear.
Highlights
It is estimated that bacterial infections of the middle ears, acute otitis media, affect 80% of the human population, usually at some point in their early lives (Bluestone and Doyle, 1988; Alsarraf et al, 1999; Monasta et al, 2012; Vos et al, 2016; Liese et al, 2014; DeAntonio et al, 2016; Tong et al, 2018)
Obtaining a more direct mechanistic understanding of the host–pathogen interactions of middle ear infections has been problematic with the lack of models that provide a means to study the progression of natural disease—i.e., initial colonization, infection, and disease resolution
Bordetella bronchiseptica, a naturally adapted respiratory tract pathogen in many mammals (Dewan and Harvill, 2019) that is well studied in the respiratory tracts of laboratory mice, infects their middle ears
Summary
It is estimated that bacterial infections of the middle ears, acute otitis media, affect 80% of the human population, usually at some point in their early lives (Bluestone and Doyle, 1988; Alsarraf et al, 1999; Monasta et al, 2012; Vos et al, 2016; Liese et al, 2014; DeAntonio et al, 2016; Tong et al, 2018). Immune Mechanism in Middle Ear Infections models to study otitis media (Piltcher et al, 2002; Melhus and Ryan, 2013; Park and Lee, 2013; Davidoss et al, 2018). To overcome this limitation, pathogens are injected directly into their middle ears to establish infections (Park and Lee, 2013). Despite the biological caveats and technical challenges, direct middle ear inoculations have been productively used to establish and study complex aspects of middle ear infections (Babl et al, 2002; Bouchet et al, 2003; Novotny et al, 2021) and remain the leading approach to gain insight into the innate immune mechanisms of host response and pathogen-specific aspects of middle ear infection (Schilder et al, 2016)
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