A model of chronic, transmissible Otitis Media in mice

Autor: Laura L. Campos, Shannon M. Wagner, Longhuan Ma, Valerie E. Ryman, Amanda L. Skarlupka, Kalyan K. Dewan, Eric T. Harvill, Uriel Blas-Machado, Brian T. Faddis, Monica Cartelle Gestal, Dawn L. Taylor-Mulneix
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: PLoS Pathogens, Vol 15, Iss 4, p e1007696 (2019)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: Infection and inflammation of the middle ears that characterizes acute and chronic otitis media (OM), is a major reason for doctor visits and antibiotic prescription, particularly among children. Nasopharyngeal pathogens that are commonly associated with OM in humans do not naturally colonize the middle ears of rodents, and experimental models in most cases involve directly injecting large numbers of human pathogens into the middle ear bullae of rodents, where they induce a short-lived acute inflammation but fail to persist. Here we report that Bordetella pseudohinzii, a respiratory pathogen of mice, naturally, efficiently and rapidly ascends the eustachian tubes to colonize the middle ears, causing acute and chronic histopathological changes with progressive decrease in hearing acuity that closely mimics otitis media in humans. Laboratory mice experimentally inoculated intranasally with very low numbers of bacteria consistently have their middle ears colonized and subsequently transmit the bacterium to cage mates. Taking advantage of the specifically engineered and well characterized immune deficiencies available in mice we conducted experiments to uncover different roles of T and B cells in controlling bacterial numbers in the middle ear during chronic OM. The iconic mouse model provides significant advantages for elucidating aspects of host-pathogen interactions in otitis media that are currently not possible using other animal models. This natural model of otitis media permits the study of transmission between hosts, efficient early colonization of the respiratory tract, ascension of the eustachian tube, as well as colonization, pathogenesis and persistence in the middle ear. It also allows the combination of the powerful tools of mouse molecular immunology and bacterial genetics to determine the mechanistic basis for these important processes.
Author summary Bacterial infections of the middle ears (otitis media), particularly among children, is a global problem, causing fever, pain, conductive hearing loss and possible complications due to persistence/recurrence. Current understanding is poor, and advances are slowed by limitations of experimental systems that, for example, inject large numbers of human pathogens into the middle ears of rodents. Such approaches introduce tissue damage, bypass progression from natural colonization to disease and these pathogens fail to persist as chronic infections, the period when complications associated with otitis media begin to increase. Here we report that Bordetella pseudohinzii, a gram-negative bacterium we previously identified as a respiratory pathogen of mice, naturally and extremely efficiently colonizes and persists in their middle ears, causing acute and chronic histopathological changes that closely mimic otitis media in humans. Laboratory mice experimentally infected with low bacterial numbers by droplet inhalation consistently have their middle ears colonized and subsequently transmit the bacterium to cage mates. The natural B. pseudohinzii-mouse model provides an experimental system in which to study aspects of the progression from earliest colonization, infection, spread, pathogenesis to long-term persistence as well as providing the tools of immune-deficient mice that can reveal the contributions of each aspect of immunity in controlling and clearing chronic middle ear infection.
Databáze: OpenAIRE
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