Effect of indoleamine dioxygenase-1 deficiency and kynurenine pathway inhibition on murine cerebral malaria |
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| Authors: | Jenny Miu Helen J. Ball Nicholas H. Hunt |
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| Affiliation: | a Molecular Immunopathology Unit, Bosch Institute and School of Medical Sciences, Medical Foundation Building (K25), University of Sydney, Sydney, NSW 2006, Australia
b Institute of Molecular Medicine and Genetics, Medical College of Georgia, CA, USA |
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| 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. |
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| Keywords: | Cerebral malaria Indoleamine 2,3-dioxygenase Kynurenic acid Kynurenine pathway Picolinic acid Quinolinic acid Tryptophan metabolism |
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