Effect of indoleamine dioxygenase-1 deficiency and kynurenine pathway inhibition on murine cerebral malaria

Jenny Miu, Helen J. Ball, Andrew L. Mellor, Nicholas H. Hunt

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Cerebral malaria (CM) can be a fatal manifestation of Plasmodium falciparum infection. In this study, two different approaches were used to examine the role of indoleamine 2,3-dioxygenase-1 (IDO-1) and its metabolites in the development of murine CM. Mice genetically deficient in IDO-1 were not protected against CM, but partial protection was observed in C57BL/6 mice treated with Ro 61-8048, an inhibitor of kynurenine-3-hydroxylase. This protection was associated with suppressed levels of picolinic acid (PA) within the brain, but not with changes in the levels of kynurenic acid (KA) or quinolinic acid (QA). These data suggest that although IDO-1 is not directly involved in the pathogenesis of CM in C57BL/6 mice, the production of the kynurenine pathway metabolite PA may contribute to the development of murine CM.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalInternational Journal for Parasitology
Volume39
Issue number3
DOIs
StatePublished - Feb 1 2009

Keywords

  • Cerebral malaria
  • Indoleamine 2,3-dioxygenase
  • Kynurenic acid
  • Kynurenine pathway
  • Picolinic acid
  • Quinolinic acid
  • Tryptophan metabolism

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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