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

doi:10.1016/j.ijpara.2008.10.005

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

Infectious Disease

Research output: Contribution to journal › Article › peer-review

22 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 language	English (US)
Pages (from-to)	363-370
Number of pages	8
Journal	International Journal for Parasitology
Volume	39
Issue number	3
DOIs	https://doi.org/10.1016/j.ijpara.2008.10.005
State	Published - Feb 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ijpara.2008.10.005

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title = "Effect of indoleamine dioxygenase-1 deficiency and kynurenine pathway inhibition on murine cerebral malaria",

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.",

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

author = "Jenny Miu and Ball, {Helen J.} and Mellor, {Andrew L.} and Hunt, {Nicholas H.}",

note = "Funding Information: We thank Cacang Suarna for help with the KA assays. This work was supported by Grants from the National Health and Medical Research Council of Australia and Australian Research Council to NH. JM was supported by an Australian Postgraduate Award. HB was a Rolf Edgar Lake Research Fellow of the Faculty of Medicine, University of Sydney. ",

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AU - Hunt, Nicholas H.

N1 - Funding Information: We thank Cacang Suarna for help with the KA assays. This work was supported by Grants from the National Health and Medical Research Council of Australia and Australian Research Council to NH. JM was supported by an Australian Postgraduate Award. HB was a Rolf Edgar Lake Research Fellow of the Faculty of Medicine, University of Sydney.

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N2 - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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