Innate immunity in otitis media

Otitis media (OM) is the most prevalent childhood disease in developed countries. The involvement of innate immunity mediated by Toll-like receptors (TLRs) in OM pathophysiology has been implicated primarily by studies in cell lines and by association studies of linking polymorphisms of genes involved in innate immunity with OM prevalence. However, the precise role of innate immunity in OM is incompletely understood. To address this, we investigated the middle ear (ME) response to non-typeable Haemophilus influenzae (NTHi) in a mouse model. Using cDNA microarrays, real-time PCR and gene deletion mice, we assessed the expression of innate immune genes during OM and their contributions to pathogenesis and recovery. Innate immunity is mediated by the interaction of pathogen molecules with receptors such as the TLRs, leading to the activation of adaptor molecules and, ultimately, the production of pro-inflammatory cytokines. We observed the upregulation of genes throughout the TLR pathway. Moreover, deletion of key innate immune genes resulted in marked prolongation of OM, coupled with an inability to clear NTHi. These results demonstrate that innate immune signalling mediated by TLRs is critical to the regulation of infection in NTHi-induced OM, and that intact innate immunity is required for recovery.