免疫应答所致的中耳组织不可逆损伤是中耳炎损害患者听力的主要原因。本课题组在建立了肺炎链球菌中耳炎小鼠模型的基础上，发现IL-17a在启动固有免疫应答和组织损伤中可能具有"双刃剑"作用，造成免疫应答和组织损伤失衡，但具体机制尚不清楚。 本项目拟借助缺陷小鼠模型、原代细胞模型，采用荧光定量PCR、功能分类表达谱芯片、western blot、流式细胞术、激光共聚焦等技术，从以下3方面进行研究：寻找中耳微环境中识别菌体成分的模式识别受体（PRR）；筛选激活IL-17a释放的信号传导通路；探讨IL-17a启动固有免疫应答和造成中耳组织免疫损伤的分子机制。最终绘制出"PRR识别-信号传导通路激活-IL-17a释放-固有免疫应答和组织损伤失衡"的机制图谱。 本研究不仅能阐明IL-17a在肺炎链球菌中耳炎致病机制中的作用，还能阐明免疫应答和组织损伤失衡致儿童听力损伤的机制,为中耳炎的治疗提供新思路。

In otitis media (OM), the irreversible middle ear tissue injury during the course of immune response is the key factor leading to hearing loss or even deafness. Based on the C57BL/6 mice model infected by S.pn, the most important bacterial pathogen associated with OM, our research group has firstly discovered that IL-17a, a major pro-inflammatory factor, played the role of a double-edged sword by breaking the balance between immune response and tissue injury. However, the mechanism of causing such an imbalance remains unclear. Techniques such as real-time PCR, expression spectrum genechips, western blot,flow cytometry and laser scanning confocal microscope will be used.Based on the knockout mice models and primary cells models, we propose to research the following three aspects. The first step is to find out the pattern-recognition receptors of S.pn, then to identify the signal transduction pathways of IL-17a release, and therefore to clarify the molecular mechanism of innate immune response and tissue injury mediated by IL-17a. Our final goal is to map out the mechanism of "recognition by the pattern-recognition receptors-activation of signal transduction pathways-release of IL-17a-imbalance between innate immune response and tissue injury". This research can not only unveil the potential role of IL-17a in S.pn OM pathogenesis, but also might contribute to clarify the mechanism of hearing loss due to the imbalance between immune response and tissue injury, providing new ideas of therapy for OM.