{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T03:29:46Z","timestamp":1771385386727,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012651","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000}}],"reference-count":95,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T00:00:00Z","timestamp":1729209600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI132146"],"award-info":[{"award-number":["T32AI132146"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI148241"],"award-info":[{"award-number":["R01AI148241"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI178106"],"award-info":[{"award-number":["R01AI178106"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20GM125504"],"award-info":[{"award-number":["P20GM125504"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Jewish Heritage Foundation"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Leukotriene B4 (LTB<jats:sub>4<\/jats:sub>) is an inflammatory lipid produced in response to pathogens that is critical for initiating the inflammatory cascade needed to control infection. However, during plague, <jats:italic>Yersinia pestis<\/jats:italic> inhibits the timely synthesis of LTB<jats:sub>4<\/jats:sub> and subsequent inflammation. Using bacterial mutants, we previously determined that <jats:italic>Y<\/jats:italic>. <jats:italic>pestis<\/jats:italic> inhibits LTB<jats:sub>4<\/jats:sub> synthesis via the action of the Yop effector proteins that are directly secreted into host cells through a type 3 secretion system (T3SS). Here, we show that the T3SS is the primary pathogen associated molecular pattern (PAMP) required for production of LTB<jats:sub>4<\/jats:sub> in response to both <jats:italic>Yersinia<\/jats:italic> and <jats:italic>Salmonella<\/jats:italic>. However, we also unexpectantly discovered that T3SS-mediated LTB<jats:sub>4<\/jats:sub> synthesis by neutrophils and macrophages require the activation of two distinctly different host signaling pathways. We identified that phagocytosis and the NLRP3\/CASP1 inflammasome significantly impact LTB<jats:sub>4<\/jats:sub> synthesis by macrophages but not neutrophils. Instead, the SKAP2\/PLC signaling pathway is required for T3SS-mediated LTB<jats:sub>4<\/jats:sub> production by neutrophils. Finally, while recognition of the T3SS is required for LTB<jats:sub>4<\/jats:sub> production, we also discovered that a second unrelated PAMP-mediated signal activates the MAP kinase pathway needed for synthesis. Together, these data demonstrate significant differences in the host factors and signaling pathways required by macrophages and neutrophils to quickly produce LTB<jats:sub>4<\/jats:sub> in response to bacteria. Moreover, while macrophages and neutrophils might rely on different signaling pathways for T3SS-dependent LTB<jats:sub>4<\/jats:sub> synthesis, <jats:italic>Y<\/jats:italic>. <jats:italic>pestis<\/jats:italic> has evolved virulence mechanisms to counteract this response by either leukocyte to inhibit LTB<jats:sub>4<\/jats:sub> synthesis and colonize the host.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012651","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T17:36:54Z","timestamp":1729273014000},"page":"e1012651","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Distinct mechanisms of type 3 secretion system recognition control LTB4 synthesis in neutrophils and macrophages"],"prefix":"10.1371","volume":"20","author":[{"given":"Amanda","family":"Brady","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo C.","family":"Mora Martinez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Hammond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaitlyn M.","family":"Whitefoot-Keliin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bodduluri","family":"Haribabu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia M.","family":"Uriarte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1505-5429","authenticated-orcid":true,"given":"Matthew B.","family":"Lawrenz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,10,18]]},"reference":[{"issue":"2","key":"ppat.1012651.ref001","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1189\/jlb.0811402","article-title":"Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation","volume":"91","author":"CD Sadik","year":"2012","journal-title":"J Leukoc Biol"},{"issue":"5","key":"ppat.1012651.ref002","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.devcel.2012.02.003","article-title":"LTB4 is a signal-relay molecule during neutrophil chemotaxis","volume":"22","author":"PV Afonso","year":"2012","journal-title":"Dev Cell"},{"issue":"2","key":"ppat.1012651.ref003","doi-asserted-by":"crossref","first-page":"589","DOI":"10.4049\/jimmunol.174.2.589","article-title":"Leukotrienes: Underappreciated mediators of innate immune 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