TLR2 promotes macrophage recruitment and Streptococcus pneumoniae clearance during mouse otitis media

Abstract

Background:The natural course of otitis media (OM) in most children is acute and self-limiting; however, approximately 10-20% of children can experience persistent or recurrent OM. Determining the host factors that influence outcome of OM will help us design better therapies. This study focused on the role of Toll-like receptor 2 (TLR2) in a pneumococcal OM mouse model.Methods:The middle ears (MEs) of wild-type (WT) and TLR2 -/- mice were inoculated with Streptococcus pneumoniae (Spn) serotype 19F via transbullar injection. ME TLR2 expression in WT mice was determined by qRT-PCR and immunofluorescence. ME pathological manifestations, inflammatory response, and pneumococcal clearance between WT and TLR2 -/- mice were compared after Spn inoculation.Results:TLR2 expression in ME mucosa was markedly enhanced following infection with Spn in WT mice. In contrast to WT mice, TLR2 -/- mice exhibited unaffected early ME inflammatory response. During late stage of ME infection, however, the absence of TLR2 can lead to reduced macrophage recruitment, impaired Spn clearance, and prolonged ME inflammation.Conclusion:Our results demonstrate that TLR2 signaling is critical for bacterial clearance and timely resolution of inflammation in OM induced by Spn.