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Trypanosomes have evolved many immune-evasion mechanisms to facilitate their own survival, as well as prolonging host survival to ensure completion of the parasitic life cycle. A key feature of the bloodstream form of T. brucei is the secretion of aromatic keto acids, which are metabolized from tryptophan. In this study, we describe an immunomodulatory role for one of these keto acids, indole-3-pyruvate (I3P). We demonstrate that I3P inhibits the production of PGs in activated macrophages. We also show that, despite the reduction in downstream PGs, I3P augments the expression of cyclooxygenase (COX2). This increase in COX2 expression is mediated in part via inhibition of PGs relieving a negative-feedback loop on COX2. Activation of the aryl hydrocarbon receptor also participates in this effect. However, the increase in COX2 expression is of little functionality, as we also provide evidence to suggest that I3P targets COX activity. This study therefore details an evasion strategy by which a trypanosome-secreted metabolite potently inhibits macrophage-derived PGs, which might promote host and trypanosome survival.<\/jats:p>","DOI":"10.4049\/jimmunol.2100402","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T16:46:05Z","timestamp":1633970765000},"page":"2551-2560","source":"Crossref","is-referenced-by-count":18,"title":["The Trypanosome-Derived Metabolite Indole-3-Pyruvate Inhibits Prostaglandin Production in Macrophages by Targeting COX2"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8069-8474","authenticated-orcid":false,"given":"Ciana","family":"Diskin","sequence":"first","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7562-0314","authenticated-orcid":false,"given":"Sarah E","family":"Corcoran","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-118X","authenticated-orcid":false,"given":"Victoria J","family":"Tyrrell","sequence":"additional","affiliation":[{"name":"Systems Immunity Research Institute, School of Medicine, Cardiff University , Cardiff ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne F","family":"McGettrick","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zbigniew","family":"Zaslona","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie B","family":"O\u2019Donnell","sequence":"additional","affiliation":[{"name":"Systems Immunity Research Institute, School of Medicine, Cardiff University , Cardiff ,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3742-4304","authenticated-orcid":false,"given":"Derek P","family":"Nolan","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A J","family":"O\u2019Neill","sequence":"additional","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College , Dublin ,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"2025022610322746700_r1","doi-asserted-by":"crossref","first-page":"e0005585","DOI":"10.1371\/journal.pntd.0005585","article-title":"Monitoring the elimination of human African trypanosomiasis: update to 2014","volume":"11","author":"Franco","year":"2017","journal-title":"PLoS Negl. 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