biostudies-literatureUnknown46(1)Gong Z<i>Staphylococcus aureus</i> (<i>S. aureus</i>) 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 <i>S. aureus</i>-induced bovine mastitis from both host and pathogen perspectives, focusing on prostaglandin E₂ (PGE₂) as a key regulator. During bovine mastitis, macrophages were recruited into the mammary gland with elevated inflammatory mediators. <i>S. aureus</i> lipoproteins amplified inflammation by activating MAPK and NF-κB pathways <i>via</i> TLR2, TLR4, and NLRP3, leading to elevated secretion of mediators, including PGE₂, in bBMMs. Inhibition of TLR2, TLR4, or NLRP3 decreased COX-2 and mPGES-1 expreThe veterinary quarterly2615759https://www.ebi.ac.uk/biostudies/studies/S-EPMC12818336biostudies-literatureAn underlying mechanism of bovine mastitis: PGE&lt;sub&gt;2&lt;/sub&gt; regulates &lt;i&gt;Staphylococcus aureus&lt;/i&gt;-induced inflammatory response through TLR2, TLR4, and NLRP3 in macrophages.PMC12818336Gao RRen PBao WShuang FGong ZYu ZZhang SWang YZhao JQin SfalseAn underlying mechanism of bovine mastitis: PGE&lt;sub&gt;2&lt;/sub&gt; regulates &lt;i&gt;Staphylococcus aureus&lt;/i&gt;-induced inflammatory response through TLR2, TLR4, and NLRP3 in macrophages.<i>Staphylococcus aureus</i> (<i>S. aureus</i>) 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 <i>S. aureus</i>-induced bovine mastitis from both host and pathogen perspectives, focusing on prostaglandin E₂ (PGE₂) as a key regulator. During bovine mastitis, macrophages were recruited into the mammary gland with elevated inflammatory mediators. <i>S. aureus</i> lipoproteins amplified inflammation by activating MAPK and NF-κB pathways <i>via</i> TLR2, TLR4, and NLRP3, leading to elevated secretion of mediators, including PGE₂, in bBMMs. Inhibition of TLR2, TLR4, or NLRP3 decreased COX-2 and mPGES-1 expre2026-01-01T00:00:00Z2026 Dec2026-06-06T17:56:21.155Z2026-06-04T03:08:51.936ZS-EPMC128183364154649910.1080/01652176.2026.2615759