Viral infections as gatekeepers of bacterial infections in otitis media: Immune mechanisms and implications for therapeutic interventions

Otitis media (OM) is a highly prevalent inflammatory disease of the human middle ear and a key contributor to poor health outcomes in young children on a global scale. While bacterial pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis are well-recognised contributors to OM, increasing evidence highlights respiratory viruses as critical gatekeepers that predispose the middle ear to bacterial infection. Viral upper respiratory infections initiate mucosal inflammation, disrupt epithelial barrier integrity and mucociliary clearance, and alter host immunological responses. Collectively, these changes create a permissive environment for bacterial colonization, ascension, and persistence within the middle ear. Viral and bacterial coinfections are commonly found and are linked to poorer clinical outcomes, extended inflammation, and increased disease severity. This review synthesises current evidence on the mechanisms by which viruses prime the middle ear for subsequent bacterial infections, with particular emphasis on epithelial dysfunction, receptor modulation, interferon-driven immune responses, and alterations in innate immune training. Furthermore, it discusses the translational implications of viral-bacterial interactions for the development of improved diagnostic, therapeutic, and preventive strategies, including antivirals and vaccines, in the context of polymicrobial disease dynamics. A clear understanding of these interactions is crucial for advancing improved interventions to lower the global burden of OM.