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The Trypanosome-Derived Metabolite Indole-3-Pyruvate Inhibits Prostaglandin Production in Macrophages by Targeting COX2.
Diskin, Ciana; Corcoran, Sarah E; Tyrrell, Victoria J; McGettrick, Anne F; Zaslona, Zbigniew; O'Donnell, Valerie B; Nolan, Derek P; O'Neill, Luke A J.
Afiliación
  • Diskin C; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; and.
  • Corcoran SE; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; and.
  • Tyrrell VJ; Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, United Kingdom.
  • McGettrick AF; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; and.
  • Zaslona Z; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; and.
  • O'Donnell VB; Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, United Kingdom.
  • Nolan DP; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; and.
  • O'Neill LAJ; School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; and laoneill@tcd.ie.
J Immunol ; 207(10): 2551-2560, 2021 11 15.
Article en En | MEDLINE | ID: mdl-34635586
The protozoan parasite Trypanosoma brucei is the causative agent of the neglected tropical disease human African trypanosomiasis, otherwise known as sleeping sickness. 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.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Tripanosomiasis Africana / Prostaglandinas / Ciclooxigenasa 2 / Indoles / Macrófagos Límite: Animals / Humans Idioma: En Revista: J Immunol Año: 2021 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Tripanosomiasis Africana / Prostaglandinas / Ciclooxigenasa 2 / Indoles / Macrófagos Límite: Animals / Humans Idioma: En Revista: J Immunol Año: 2021 Tipo del documento: Article