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Probing Immune-Mediated Clearance of Acute Middle Ear Infection in Mice
Kalyan K Dewan1, Colleen Sedney1, Amanda D Caulfield1
1Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, United States.
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.
Insights
A novel mouse model using Bordetella bronchiseptica effectively mimics acute otitis media (AOM). This model highlights the crucial roles of T and B cells in clearing middle ear infections, differing from respiratory immunity.
Area of Science:
- Immunology
- Microbiology
- Otolaryngology
Background:
- Acute otitis media (AOM) is a common middle ear infection often caused by nasopharyngeal bacteria ascending the Eustachian tube.
- Current AOM models involve direct injection or viral co-infections, limiting understanding of natural disease processes.
Purpose of the Study:
- To establish a flexible mouse model for studying naturally occurring AOM.
- To investigate the roles of T and B cells in resolving middle ear infections.
- To explore differences between respiratory and middle ear immunology.
Main Methods:
- Utilized *Bordetella bronchiseptica*, a respiratory pathogen, to colonize the middle ear via Eustachian tube ascent in mice.
- Assessed infection resolution in mice lacking T and/or B cells.
- Evaluated the protective efficacy of adoptively transferred antibodies in the lungs versus middle ears.
Main Results:
- *Bordetella bronchiseptica* efficiently colonizes the mouse middle ear, establishing a natural AOM model.
- Mice deficient in T and/or B cells were unable to clear middle ear infections.
- Antibodies protected lungs but only partially protected middle ears, indicating distinct immune responses.
Conclusions:
- The *Bordetella bronchiseptica* mouse model offers a valuable system for dissecting AOM pathogenesis.
- Both T and B cells are essential for clearing middle ear infections.
- Middle ear immunity differs significantly from respiratory immunity, particularly concerning antibody efficacy.
