奶牛乳腺感染可导致乳蛋白产量降低，然而乳腺感染导致乳蛋白含量降低的分子机制尚不清晰。本项目在认识奶牛乳腺天然免疫以及乳蛋白合成调控网络基础上，聚焦于奶牛乳腺感染时TLRs/NF-κB信号通路与PI3K-Akt-mTOR信号通路的交互作用，以及SOCS分子可能参与介导乳腺上皮细胞PRL、GH和胰岛素抵抗上。在体研究奶牛乳腺自然感染和实验性感染条件下TLRs/NF-κB、PI3K-Akt-mTOR、SOCS、JAK-STAT信号通路、炎性细胞因子水平及乳蛋白合成情况的变化；体外研究干预相关信号通路对实验性感染乳腺上皮细胞其它信号通路的时序表达差异、相互作用，炎性细胞因子、乳蛋白合成水平，以及SOCS表达水平与PRL、GH和胰岛素抵抗的相关性。以期揭示乳腺感染导致乳蛋白产量降低的信号转导机制，为深入研究乳蛋白合成调控机制提供科学依据，为通过人工干预手段来提高牛奶营养品质奠定研究基础。

Bovine mammary infection can lead to milk composition changes and milk protein decrease and result in a major economic impact in the dairy industry. However, the underlying mechanism of mammary infection induced milk protein depression remains unclear. We hypothesize that the crosstalk between the TLRs/NF-κB and mTOR pathways, the SOCS and JAK-STAT pathways may have a potential role in mammary infection induced milk protein depression in dairy cows based on the theory of milk protein synthesis and the innate immune response of bovine mammary gland to E. coli and S. aureus. The project will use western blotting, real-time RT-PCR, ELISA, EMSA and other methods to characterize the sequential change of the crosstalk between the TLRs/NF-κB and mTOR pathways, the SOCS and JAK-STAT pathways, the transcriptional activity of NF-κB and STAT5, the expression of pro-inflammation cytokine and milk protein genes in dairy cow and mammary epithelial cells after LPS/LTA challenge so as to identify the signal transduction pathway in mammary infection induced milk protein depression in dairy cows. These results will provide scientific basis to further study the regulatory mechanism of milk protein synthesis of and improve the nutritional quality of cow's milk.