An infant mouse model of influenza-drivennontypeable Haemophilus influenzaecolonization and acute otitis media suitable for preclinical testing of novel therapies

Katherine R. Landwehr, Caitlyn M. Granland, Kelly M. Martinovich, Naomi M. Scott, Elke J. Seppanen, Luke Berry, Deborah Strickland, Alma Fulurija, Peter C. Richmond, Lea Ann S. Kirkham

Research output: Contribution to journalArticlepeer-review

Abstract

Nontypeable Haemophilus influenzae(NTHi) is a major otitis media (OM) pathogen, with colonization a prerequisite for disease development. Most acute OM is in children <5 years old, with recurrent and chronic OM impacting hearing and learning. Therapies to prevent NTHi colonization and/or disease are needed, especially for young children. Respiratory viruses are implicated in driving the development of bacterial OM in children. We have developed an infant mouse model of influenza-drivenNTHi OM, as a preclinical tool for the evaluation of safety and efficacyof clinical therapies to prevent NTHi colonization and the development of OM. In this model, 100% of infant BALB/cARC mice were colonized with NTHi, and all developed NTHi OM. InfluenzaA virus (IAV) facilitated the establishment of dense (1 × 105 CFU/mL) and long-lasting (6 days) NTHi colonization. IAV was essential for the development of NTHi OM, with 100% of mice in the IAV/NTHi group developing NTHi OM compared with 8% of mice in the NTHi only group. Histological analysis and cytokine measurements revealed that the inflammationobserved in the middle ear of the infant mice with OM reflectedinflammationobserved in children with OM. We have developed the firstinfant mouse model of NTHi colonization and OM. This ascension model uses influenza-drivenestablishment of OM and reflectsthe clinical pathology of bacterial OM developing after a respiratory virus infection. This model provides a valuable tool for testing therapies to prevent or treat NTHi colonization and disease in young children.

Original languageEnglish
Number of pages13
JournalInfection and Immunity
Volume92
Issue number5
DOIs
Publication statusPublished - May 2024

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