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Inflammatory processes are regulated by distinct lipid mediators (LMs) but how their biosynthetic pathways are orchestrated in <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> infections is elusive. We show that <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> strikingly not only modulates pro\u2010inflammatory, but also inflammation\u2010resolving LM pathways in murine osteomyelitis and osteoclasts as well as in human monocyte\u2010derived macrophages (MDMs) with different phenotype. Targeted LM metabololipidomics using ultra\u2010performance liquid chromatography\u2010tandem mass spectrometry revealed massive generation of LM with distinct LM signature profiles in acute and chronic phases of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>\u2010induced murine osteomyelitis in vivo. In human MDM, <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> elevated cyclooxygenase\u20102 (COX\u20102) and microsomal prostaglandin E<jats:sub>2<\/jats:sub>\u00a0synthase\u20101 (mPGES\u20101), but impaired the levels of 15\u2010lipoxygenase\u20101 (15\u2010LOX\u20101), with respective changes in LM signature profiles initiated by these enzymes, that is, elevated PGE<jats:sub>2<\/jats:sub> and impaired specialized pro\u2010resolving mediators, along with reduced M2\u2010like phenotypic macrophage markers. The cell wall component, lipoteichoic acid (LTA), mimicked the impact of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> elevating COX\u20102\/mPGES\u20101 expression via NF\u2010\u03baB and p38\u00a0MAPK signalling in MDM, while the impairment of 15\u2010LOX\u20101 correlates with reduced expression of Lamtor1. In conclusion, <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> dictates LM pathways via LTA resulting in a shift from anti\u2010inflammatory M2\u2010like towards pro\u2010inflammatory M1\u2010like LM signature profiles.<\/jats:p>","DOI":"10.1111\/imm.13449","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T15:49:35Z","timestamp":1644508175000},"page":"47-67","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>Staphylococcus aureus<\/i> controls eicosanoid and specialized pro\u2010resolving mediator production via lipoteichoic acid"],"prefix":"10.1111","volume":"166","author":[{"given":"Laura","family":"Miek","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical\/Medicinal Chemistry Institute of Pharmacy Friedrich\u2010Schiller\u2010University Jena  Jena 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