Otitis media induced by peptidoglycan-polysaccharide (PGPS) in TLR2-deficient (Tlr2-/-) mice for developing drug therapy

Background: Toll like receptor 2 (TLR2) signaling can regulate the pathogenesis of otitis media (OM). However, the precise role of TLR2 signaling in OM has not been clarified due to the lack of an optimal animal model. Peptidoglycan-polysaccharide (PGPS) of the bacterial cell wall can induce inflammation by activating the TLR2 signaling. This study aimed at examining the pathogenic characteristics of OM induced by PGPS in TIr2(-/-) mice, and the potential therapeutic effect of sodium aescinate (SA) in this model. Methods: Wild-type (WT) and TIr2(-/-) mice were inoculated with streptococcal PGPS into their middle ears (MEs) and treated intravenously with vehicle or SA daily beginning at 3 days prior to PGPS for 6 consecutive days. The pathologic changes of individual mice were evaluated longitudinally. Results: In comparison with WT mice, T1r2(-/-) mice were susceptible to PGPS-induced OM. Tlr2(-/-) mice displayed greater hearing loss, tympanic membrane damage, ME mucosal thickening, longer inflammation state, cilia and goblet cell loss. SA-treatment decreased neutrophil infiltration, modulated TLR2-related gene expression and improved ciliary organization. Conclusions: PGPS induced a relatively stable OM in TIr2(-/-) mice, providing a new model for OM research. Treatment with SA mitigated the pathogenic damage in the ME and may be valuable for intervention of OM. (C) 2015 Elsevier B.V. All rights reserved.