鸡源抗菌肽CATH-2抑制禽致病性大肠杆菌诱导炎症小体活化的分子机制研究

Cathelicidins是宿主体内自身分泌的具有抗感染和免疫调节活性的宿主防御肽。申请人前期研究发现，鸡源Cathelicidins (CATH-2)抑制禽致病性大肠杆菌（APEC）诱导IL-1β的分泌。IL-1β是NLRP3炎症小体激活的主要效应分子，因此CATH-2可能抑制NLRP3炎症小体的活化，但是具体的分子机制尚不清楚。本项目拟采用APEC体内外感染模型，通过体外细胞实验研究CATH-2抑制APEC诱导NLRP3炎症小体的激活及IL-1β的成熟与分泌，明确CATH-2作用于NLRP3炎症小体通路中的靶向分子及具体位点，最后通过体内感染实验研究CATH-2在APEC感染中的抗炎作用。本研究旨在阐明CATH-2抑制APEC诱导炎症小体活化的分子机制，将为深入理解该类抗菌肽的免疫调控机制奠定基础，也将为抗感染及免疫调节候选药物的开发应用提供数据支撑。

Cathelicidins are host defense peptides with antimicrobial and immunomodulatory activities. Our previous study showed that chicken cathelicidin-2 (CATH-2) inhibited avian pathogenic E. coli (APEC)-induced secretion of IL-1β, which is the key effector of NLRP3 activation, indicating that CATH-2 may inhibit APEC-induced activation of NLRP3. However, the molecular mechanism is still unclear. Therefore, APEC-infected macrophages will be used to investigate that CATH-2 inhibits APEC-induced activation of NLRP3 as well as maturation and secretion of IL-1β. Then, the target molecule and site interacting with CATH-2 will be clarified in NLRP3 inflammasome pathway. Finally, anti-inflammatory activity of CATH-2 will be studied in APEC-infected chicken. This study aims to explore the molecular mechanism that CATH-2 inhibits APEC-induced activation of inflammasome, which contributes to the further understanding on immune regulation mechanism of cathelicidins and also provides data support for the development of the possible use of cathelicidins as anti-infective and immunomodulatory medicine candidates.