Toll-Spӓtzle信号通路是先天免疫系统的重要组成部分。果蝇含有9个Toll和6个Spӓtzle（Spz）蛋白，只有经典的Toll-1-Spz-1信号通路在免疫和发育中的功能得到深入研究，其他Toll受体以及Spӓtzle配体在免疫中的功能鲜有报道。我们发现果蝇的Toll-1和Toll-7在体外可与多个Spz结合并激活抗菌肽基因drosomycin，而且Toll-1和Toll-7突变体对不同病原微生物的抵抗力存在差异。为此，本项目将研究果蝇体内多种Toll-Spz复合物在抵抗不同病原微生物侵染中的功能和机制。研究内容包括：①果蝇体内多种Toll-Spz复合物的鉴定和形成特征；②这些复合物在果蝇抵抗不同病原微生物感染中的功能；③Toll-1和Toll-7复合物调控下游免疫信号通路的分子机制。本项目的研究成果将拓展Toll-Spz信号通路在免疫中的功能，为昆虫及动物免疫研究提供新思路。

The Toll-Spӓtzle pathway plays a critical role in the innate immune system. Drosophila genome encodes 9 Tolls and 6 Spätzle (Spz) proteins, but only the functions of the canonical Toll-1-Spz-1 pathway in innate immunity and development have been well studied. Toll-2 to Toll-9 may play a role in immune responses, but functions of Spz-2 to Spz-6 as ligands of Tolls in innate immunity are largely unknown. Our preliminary data showed that both Toll-1 and Toll-7 interacted with Spz-1, Spz-2 and Spz-5 in vitro, and multiple Toll-1-Spz and Toll-7-Spz complexes activated drosomycin promoter. More importantly, we showed that Toll-1 and Toll-7 mutant flies responded differently to septic infection by bacteria, fungus and virus, indicating different effects of multiple Toll-1-Spz and Toll-7-Spz complexes in Drosophila innate immunity against various pathogens. In this project, we will investigate the formation of Toll-1-Spz and Toll-7-Spz complexes in flies, the relationship between the Toll-Spz complexes and various pathogen infection, and the downstream signaling pathways regulated by the Toll-1-Spz and Toll-7-Spz complexes. Results from this project will broaden our knowledge about the function of Toll-Spz signaling in innate immunity, and also open up a new research direction for insect and animal Toll/Toll-like receptor signaling pathways.