An underlying mechanism of bovine mastitis: PGE 2 regulates Staphylococcus aureus -induced inflammatory response through TLR2, TLR4, and NLRP3 in macrophages

作者：Zhiguo Gong, Zhuoya Yu, Peipei Ren, Shuangyi Zhang, Ruifeng Gao, Jiamin Zhao, Yixin Wang, Shaojie Qin, Wenhui Bao, Feng Shuang · 发表于：Figshare · 年份：2026 · DOI：10.6084/m9.figshare.31114784.v1 · 研究领域：Milk Quality and Mastitis in Dairy Cows、Probiotics and Fermented Foods、Breast Lesions and Carcinomas

Staphylococcus aureus ( S. aureus ) evades host immunity by modulating macrophage functions, including immune regulation and phagocytosis, ultimately contributing to bovine mastitis. This study aimed to elucidate the molecular mechanisms of S. aureus -induced bovine mastitis from both host and pathogen perspectives, focusing on prostaglandin E 2 (PGE 2 ) as a key regulator. During bovine mastitis, macrophages were recruited into the mammary gland with elevated inflammatory mediators. S. aureus lipoproteins amplified inflammation by activating MAPK and NF-κB pathways via TLR2, TLR4, and NLRP3, leading to elevated secretion of mediators, including PGE 2 , in bBMMs. Inhibition of TLR2, TLR4, or NLRP3 decreased COX-2 and mPGES-1 expression, suppressing PGE 2 synthesis, while inhibition of COX-2 or mPGES-1 can regulate the expression of TLR2 and NLRP3, as well as the activation of MAPKs and NF-κB signaling pathways. Excess PGE 2 can regulate inflammation and phagocytosis mediated by TLR2, TLR4, and NLRP3. S. aureus lipoproteins promote PGE 2 synthesis via TLR2, TLR4, and NLRP3 signaling, while PGE 2 , in turn, modulates receptor activity, inflammation, and phagocytosis. These findings reveal crucial functional cross-talk between PGE 2 and innate immune receptors in S. aureus -induced mastitis, suggesting that targeting this interaction may provide novel therapeutic strategies.