title: A new model for non-typeable Haemophilus influenzae middle ear infection in the Junbo mutant mouse.
abstract: Acute otitis media, inflammation of the middle ear, is the most common bacterial infection in children and, as a consequence, is the most common reason for antimicrobial prescription to this age group. There is currently no effective vaccine for the principal pathogen involved, non-typeable Haemophilus influenzae (NTHi). The most frequently used and widely accepted experimental animal model of middle ear infection is in chinchillas, but mice and gerbils have also been used. We have established a robust model of middle ear infection by NTHi in the Junbo mouse, a mutant mouse line that spontaneously develops chronic middle ear inflammation in specific pathogen-free conditions. The heterozygote Junbo mouse (Jbo/+) bears a mutation in a gene (Evi1, also known as Mecom) that plays a role in host innate immune regulation; pre-existing middle ear inflammation promotes NTHi middle ear infection. A single intranasal inoculation with NTHi produces high rates (up to 90%) of middle ear infection and bacterial titres (10(4)-10(5) colony-forming units/µl) in bulla fluids. Bacteria are cleared from the majority of middle ears between day 21 and 35 post-inoculation but remain in approximately 20% of middle ears at least up to day 56 post-infection. The expression of Toll-like receptor-dependent response cytokine genes is elevated in the middle ear of the Jbo/+ mouse following NTHi infection. The translational potential of the Junbo model for studying antimicrobial intervention regimens was shown using a 3 day course of azithromycin to clear NTHi infection, and its potential use in vaccine development studies was shown by demonstrating protection in mice immunized with killed homologous, but not heterologous, NTHi bacteria.
authors.affiliation: MRC Mammalian Genetics Unit, MRC Harwell, Didcot, Oxford, OX11 0RD, UK.
authors.forename: Derek
authors.initials: D
authors.lastname: Hood
authors.affiliation: Department of Paediatrics, University of Oxford Medical Sciences Division, John Radcliffe Hospital, Oxford, OX3 9DU, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Moxon
authors.affiliation: MRC Mammalian Genetics Unit, MRC Harwell, Didcot, Oxford, OX11 0RD, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Purnell
authors.affiliation: MRC Mammalian Genetics Unit, MRC Harwell, Didcot, Oxford, OX11 0RD, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Richter
authors.affiliation: MRC Mammalian Genetics Unit, MRC Harwell, Didcot, Oxford, OX11 0RD, UK.
authors.forename: Debbie
authors.initials: D
authors.lastname: Williams
authors.affiliation: Developmental Biology Division, The Roslin Institute and Royal (Dick) School of Veterinary Studies, Easter Bush Campus, University of Edinburgh, EH25 9RG, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Azar
authors.affiliation: MRC Mammalian Genetics Unit, MRC Harwell, Didcot, Oxford, OX11 0RD, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Crompton
authors.affiliation: Mary Lyon Centre, MRC Harwell, Harwell, Didcot, Oxford, OX11 0RD, UK.
authors.forename: Sara
authors.initials: S
authors.lastname: Wells
authors.affiliation: Mary Lyon Centre, MRC Harwell, Harwell, Didcot, Oxford, OX11 0RD, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Fray
authors.affiliation: MRC Mammalian Genetics Unit, MRC Harwell, Didcot, Oxford, OX11 0RD, UK.
authors.forename: Steve D M
authors.initials: SD
authors.lastname: Brown
authors.affiliation: MRC Mammalian Genetics Unit, MRC Harwell, Didcot, Oxford, OX11 0RD, UK Developmental Biology Division, The Roslin Institute and Royal (Dick) School of Veterinary Studies, Easter Bush Campus, University of Edinburgh, EH25 9RG, UK Mary Lyon Centre, MRC Harwell, Harwell, Didcot, Oxford, OX11 0RD, UK michael.cheeseman@roslin.ed.ac.uk.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Cheeseman
mesh_terms: D000818:Animals; D017963:Azithromycin / Q000737:chemistry; D004195:Disease Models, Animal; D006192:Haemophilus Infections / Q000235:genetics / Q000382:microbiology* / Q000503:physiopathology*; D006193:Haemophilus influenzae; D006579:Heterozygote; D007113:Immunity, Innate; D007249:Inflammation; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D008863:Microspheres; D009154:Mutation; D010033:Otitis Media / Q000235:genetics / Q000382:microbiology* / Q000503:physiopathology*; D015398:Signal Transduction; D013234:Stem Cells
chemical_list: D017963:Azithromycin
keywords: Azithromycin; Immunization; Junbo mouse; Non-typeable Haemophilus influenzae; Otitis media