真菌性角膜炎是常见的致盲性眼病，过度炎症反应是造成角膜损伤的病理基础，近年研究证实TREM-1是放大炎症反应的重要启动因子。我们的前期研究证实病变角膜中TREM-1表达水平与角膜损害程度具有高度相关性，但其介导免疫炎症反应的发病机制和调控环节尚不明确。本研究建立真菌性角膜炎动物模型，在TREM-1参与及缺失背景下，观察免疫效应细胞，趋化和迁移的的时空规律，分析TREM-1与TLRs及Dectin-1表达水平的变化趋势及关联性，检测下游炎性细胞因子表达谱的改变规律，阐明TREM-1介导真菌性角膜炎免疫学发病机制。通过蛋白质芯片技术筛选TREM-1信号通路，分析差异蛋白的作用，明确TREM-1的信号传递通路和调控环节。评价免疫抑制剂FK506对TREM-1信号通路的拮抗作用及起效机制，建立分别针对TREM-1受体和信号通路的二级联动免疫治疗新模式。

Fungal infections of the cornea are an important cause of blindness and visual impairment worldwide. Excessive and unregulated inflammation after fungal infection can lead to tissue damage and corneal perforation. The Triggering Receptor Expressed on Myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, which is involved in immune response to bacterial and fungal infections, particularly by amplifying the production of pro-inflammatory cytokines by the host. The precise mechanism of TREM-1 is still remaining unclear, let alone its function in fungal keratitis. The present research using a fungal keratitis murine model has provided substantial information about the ocular immune response to fungal infection. Our study provide evidence that TREM-1 not only synergizes with TLRs in the inflammatory response to fungal infection, but also interact with other PRRs such as dectin-1. Our further investigation will focuse on the TREM-1 pathway and the interaction between TREM-1 pathway and other inflammation relating pathways, which help better understand the mechanisms by which TREM-1 activation occurs. Furthermore our findings also show FK506 has a suppress effect in both the expression of TREM-1 and in the secretion of inflammatory cytokines such as IL-1β and TNFα induced by zymosan, which indicate that FK506 can possibly be a new medication for fungal keratitis.