肠炎沙门菌是重要的食源性人兽共患病原菌，潘氏细胞（PCs）通过α-防御素等抗菌肽参与肠道抗感染，而肠炎沙门菌可抑制α-防御素的表达，但其分子调控机制未知。本项目前期研究发现肠炎沙门菌dtpA基因突变可促进PCs表达α-防御素，而抑制STAT3磷酸化会降低α-防御素的表达，那么DtpA蛋白是否通过调节STAT3的磷酸化抑制PCs表达α-防御素值得深入研究。因此，本项目以α-防御素为切入点，以DtpA蛋白为研究对象，利用纯化PCs、小肠类器官和小鼠模型探究DtpA蛋白对α-防御素表达和STAT3磷酸化的影响，明确其通过抑制STAT3磷酸化调节α-防御素表达的作用；进一步通过筛选并验证DtpA蛋白抑制STAT3磷酸化的关键信号分子并探明其作用机制，以期阐明肠炎沙门菌DtpA蛋白抑制PCs表达α-防御素的分子机制，从而加深对肠炎沙门菌侵袭和致病机制的了解，为肠炎沙门菌的防控研究提供新的理论依据。

Paneth cells (PCs) are specialized epithelia cells that play a major role in host defense to enteric pathogens infection, mainly based on secretion of antimicrobial peptides and proteins including alpha-defensin. Salmonella Enteritidis is an important foodborne zoonotic pathogen which could inhibit α-defensin expression, but the exact mechanism is unclear. Our preliminary results suggest that dtpA gene transposon-mediated mutation of Salmonella Enteritidis can promote expression of α-defensin while inhibition of STAT3 phosphorylation reduces α-defensin expression in PCs. However, the effect of DtpA in Salmonella Enteritidis on PCs α-defensin production and their regulatory mechanism in needs to be further revealed. Base on the previous study, this project uses DtpA protein to investigate the mechanism ofα-defensin expression inhibited by Salmonella Enteritidis. Firstly, the function of DtpA in regulation PCs α-defensin production by inhibition of STAT3 phosphorylation will be confirmed by purified PCs, small intestinal organoid, and mouse in vitro and in vivo. Then the signal pathways associated with DtpA inhibited α-defensin production by STAT3 phosphorylation will be screened by real time PCR and membrane-based antibody arrays, and the target signal molecules will be confirmed by specific inhibitors, GST-pull down Co-IP, and RNAi assay to explore the mechanism of DtpA protein inhibiting STAT3 phosphorylation. Overall, these studies will clarify the molecular mechanism of Salmonella Enteritidis DtpA in inhibiting of α-defensin production by PCs and provide new theoretical basis for the prevention and control of Salmonella Enteritidis.