单增李斯特菌是重要的人兽共患病原菌，该菌不仅感染家畜、家禽，还严重威胁人类健康以及公共卫生安全，被列为第四大食源性致病菌。炎症小体是固有免疫系统的组成部分，在对抗微生物感染以及炎症反应中发挥重要作用。本课题组前期研究筛选到漆黄素显著抑制单增李斯特菌溶血素（LLO）成孔活性，并抑制其炎症反应。然而，漆黄素调控炎症小体抗单增李斯特菌及LLO致炎机制尚不明确。本项目拟以炎症小体信号通路相关效应分子为切入点，通过漆黄素干预单增李斯特菌及LLO诱导体内外炎症反应，应用现代分子生物学和免疫学相关技术，分析炎症小体信号通路的关键效应蛋白及炎症细胞因子等表达的变化规律，阐明关键效应蛋白分子在单增李斯特菌及LLO诱导炎症中的作用，从分子水平揭示漆黄素调控炎症小体信号通路的作用机制，明确漆黄素抗单增李斯特菌及LLO致炎作用靶点，为漆黄素作为先导化合物进一步研发及新药靶标的筛选奠定基础。

Listeria monocytogenes, listed as the fourth pernicious food-borne bacterium, is an important zoonotic pathogen which causing severe invasive infection in livestock, fowl and human beings and threatening public hygiene safety. Inflammasomes are integral parts of innate immune system and have been proved to play a crucial role in combating bacterial infection and inflammatory responses. In our previous research, it has been shown that fisetin has significant inhibit the pore-forming activity of listeriolysinO (LLO) and has the anti-inflammatory response caused by injecting Listeria monocytogenes. However, it is still not clear that the mechanism of fisetin via regulating inflammasomes against inflammation induced by Listeria monocytogenes and LLO. Based on effector molecules in inflammasomes signaling pathway, by means of modern molecular biology and immunological techniques, in this project, the regulation of inflammatory cytokines and key effector proteins expression will be analyzed in Listeria monocytogenes or LLO caused inflammation which interfered by fisetin in vivo and in vitro, the function of the vital effector molecules will be demonstrated in the process of inflammation induced by Listeria monocytogenes and LLO, the regulatory mechanism of fisetin on inflammatory signaling will be revealed at the molecular level, and the new targets of fisetin against inflammation induced by Listeria monocytogenes and LLO will be found. It may lay the foundation for the further development and utilization of the fisetin as a lead compound and for the new drug targets screening research.