Role Of Toll-Like Receptor 2 In The Pathophysiology Of Pneumococcal Otitis Media In A Mouse Model

Background Otitis media (OM) is one of the most common pediatric infections and Streptococcus pneumonia (S.pn) is the major pathogen associated with OM. In most children, the natural course of OM is self-limiting and favorable; however, approximately 10%～20% of children experience recurrent or persistent OM which can lead to hearing loss. But the specific factors contribute to this phenomenon are remain unknown. Some clinical researches have recently suggested that genetic polymorphisms in toll-like receptor (TLR) genes are associated with recurrent and persistent OM. So, this study is designed to evaluate the pathophysiology role of TLR2 in a mouse otitis media model induced by S.pn. Methods The middle ears (MEs) of mice were inoculated with S.pn suspension via transbullar injection method. Inflammatory response and S.pn clearance process within ME of wild-type (WT) and TLR2-/- were monitored after inoculation. Results We successfully established a mouse model for OM via transbullar injection method, laying foundation for future studies of pathophysiology as well as development of novel therapies and preventive measures against OM. We found that TLR2 was constitutively expressed in healthy ME tissue and markedly enhanced following infection with S.pn. Contrast to WT mice, the early ME inflammatory response of TLR2-/- mice was not affected. During later stages of ME infection, however, the absence of TLR2 can lead to significantly impaired S.pn clearance and prolonged ME inflammation, which may be associated with the reduced recruitment of monocyte/macrophages. Conclusions These data suggest that TLR2 may play an important role in the pathogenesis and prognosis of pneumococcal OM.