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Recently, we revealed that GT blocks the formation of the chemotactic lipid mediator leukotriene (LT)B<jats:sub>4<\/jats:sub> in activated human neutrophils and monocytes, and in rodents <jats:italic>in vivo,<\/jats:italic> by directly inhibiting LTA<jats:sub>4<\/jats:sub> hydrolase. Here, we elucidated the impact of GT on LTB<jats:sub>4<\/jats:sub> biosynthesis and the entire lipid mediator networks in human M1\u2010 and M2\u2010like monocyte\u2010derived macrophages (MDMs) and in human tissue\u2010resident alveolar macrophages. In activated M1\u2010MDMs with high capacities to generate LTs, the formation of LTB<jats:sub>4<\/jats:sub> was effectively suppressed by GT, connected to attenuated macrophage phagocytic activity as well as human neutrophil movement and migration. In resting macrophages, especially in M1\u2010MDMs, GT elicited strong formation of prostaglandins, while bacterial exotoxins from <jats:italic>Staphylococcus aureus<\/jats:italic> evoked a broad spectrum of lipid mediator biosynthesis in both MDM phenotypes. We conclude that GT impairs functions of activated innate immune cells through selective suppression of LTB<jats:sub>4<\/jats:sub> biosynthesis, while GT may also prime the immune system by provoking prostaglandin formation in macrophages.<\/jats:p>","DOI":"10.1111\/imm.13857","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T13:57:01Z","timestamp":1726235821000},"page":"748-767","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["<i>Aspergillus fumigatus<\/i>\u2010derived gliotoxin impacts innate immune cell activation through modulating lipid mediator production in macrophages"],"prefix":"10.1111","volume":"173","author":[{"given":"Kerstin","family":"G\u00fcnther","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical\/Medicinal Chemistry, Institute of Pharmacy Friedrich Schiller University Jena  Jena 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