{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T06:30:27Z","timestamp":1775889027741,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011280","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T00:00:00Z","timestamp":1707177600000}}],"reference-count":112,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T00:00:00Z","timestamp":1706140800000},"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":["F31AI178999"],"award-info":[{"award-number":["F31AI178999"]}],"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":["F31AI147404"],"award-info":[{"award-number":["F31AI147404"]}],"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-S2"],"award-info":[{"award-number":["R01AI148241-S2"]}],"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":["GM127495"],"award-info":[{"award-number":["GM127495"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM127607"],"award-info":[{"award-number":["GM127607"]}],"id":[{"id":"10.13039\/100000057","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 Fund for Excellence"},{"DOI":"10.13039\/100000097","name":"National Center for Research Resources","doi-asserted-by":"publisher","award":["S10RR027926"],"award-info":[{"award-number":["S10RR027926"]}],"id":[{"id":"10.13039\/100000097","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Subverting the host immune response to inhibit inflammation is a key virulence strategy of<jats:italic>Yersinia pestis<\/jats:italic>. The inflammatory cascade is tightly controlled via the sequential action of lipid and protein mediators of inflammation. Because delayed inflammation is essential for<jats:italic>Y<\/jats:italic>.<jats:italic>pestis<\/jats:italic>to cause lethal infection, defining the<jats:italic>Y<\/jats:italic>.<jats:italic>pestis<\/jats:italic>mechanisms to manipulate the inflammatory cascade is necessary to understand this pathogen\u2019s virulence. While previous studies have established that<jats:italic>Y<\/jats:italic>.<jats:italic>pestis<\/jats:italic>actively inhibits the expression of host proteins that mediate inflammation, there is currently a gap in our understanding of the inflammatory lipid mediator response during plague. Here we used the murine model to define the kinetics of the synthesis of leukotriene B4 (LTB<jats:sub>4<\/jats:sub>), a pro-inflammatory lipid chemoattractant and immune cell activator, within the lungs during pneumonic plague. Furthermore, we demonstrated that exogenous administration of LTB<jats:sub>4<\/jats:sub>prior to infection limited bacterial proliferation, suggesting that the absence of LTB<jats:sub>4<\/jats:sub>synthesis during plague contributes to<jats:italic>Y<\/jats:italic>.<jats:italic>pestis<\/jats:italic>immune evasion. Using primary leukocytes from mice and humans further revealed that<jats:italic>Y<\/jats:italic>.<jats:italic>pestis<\/jats:italic>actively inhibits the synthesis of LTB<jats:sub>4<\/jats:sub>. Finally, using<jats:italic>Y<\/jats:italic>.<jats:italic>pestis<\/jats:italic>mutants in the Ysc type 3 secretion system (T3SS) and<jats:italic>Yersinia<\/jats:italic>outer protein (Yop) effectors, we demonstrate that leukocytes recognize the T3SS to initiate the rapid synthesis of LTB<jats:sub>4<\/jats:sub>. However, several Yop effectors secreted through the T3SS effectively inhibit this host response. Together, these data demonstrate that<jats:italic>Y<\/jats:italic>.<jats:italic>pestis<\/jats:italic>actively inhibits the synthesis of the inflammatory lipid LTB<jats:sub>4<\/jats:sub>contributing to the delay in the inflammatory cascade required for rapid recruitment of leukocytes to sites of infection.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011280","type":"journal-article","created":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T18:46:49Z","timestamp":1706208409000},"page":"e1011280","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Type 3 secretion system induced leukotriene B4 synthesis by leukocytes is actively inhibited by Yersinia pestis to evade early immune recognition"],"prefix":"10.1371","volume":"20","author":[{"given":"Amanda","family":"Brady","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katelyn R.","family":"Sheneman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda R.","family":"Pulsifer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L.","family":"Price","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor M.","family":"Garrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krishna Rao","family":"Maddipati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sobha R.","family":"Bodduluri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianmin","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nolan L.","family":"Boyd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing-Juan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shesh N.","family":"Rai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Hellmann","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":[[2024,1,25]]},"reference":[{"issue":"2","key":"ppat.1011280.ref001","first-page":"11","article-title":"The history of plague\u2013Part 1. 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Olson","year":"2019","journal-title":"Infect Immun"},{"issue":"5","key":"ppat.1011280.ref028","doi-asserted-by":"crossref","first-page":"e1004893","DOI":"10.1371\/journal.ppat.1004893","article-title":"Circumventing Y. pestis virulence by early recruitment of neutrophils to the lungs during pneumonic plague","volume":"11","author":"Y Vagima","year":"2015","journal-title":"PLoS Pathog."},{"issue":"6","key":"ppat.1011280.ref029","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.MCHD-0035-2016","article-title":"Lipid mediators in inflammation","volume":"4","author":"M Bennett","year":"2016","journal-title":"Microbiol Spectr"},{"key":"ppat.1011280.ref030","first-page":"605959","article-title":"The role of lipids mediators in inflammation and resolution","volume":"2015","author":"A de Paula Rogerio","year":"2015","journal-title":"Biomed Res 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Palace","year":"2018","journal-title":"Infect Immun"},{"issue":"12","key":"ppat.1011280.ref051","doi-asserted-by":"crossref","first-page":"e1000686","DOI":"10.1371\/journal.ppat.1000686","article-title":"Innate immune recognition of Yersinia pseudotuberculosis type III secretion.","volume":"5","author":"V Auerbuch","year":"2009","journal-title":"PLoS Pathog."},{"key":"ppat.1011280.ref052","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.mib.2015.11.001","article-title":"Yersinia versus host immunity: how a pathogen evades or triggers a protective response","volume":"29","author":"LK Chung","year":"2016","journal-title":"Curr Opin Microbiol"},{"issue":"1","key":"ppat.1011280.ref053","doi-asserted-by":"crossref","first-page":"e02095","DOI":"10.1128\/mBio.02095-14","article-title":"Inflammasome activation in response to the Yersinia type III secretion system requires hyperinjection of translocon proteins YopB and YopD","volume":"6","author":"EE 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