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Intact indoleamine 2,3-dioxygenase activity in human chronic granulomatous disease


Jürgens, B; Fuchs, D; Reichenbach, J; Heitger, A (2010). Intact indoleamine 2,3-dioxygenase activity in human chronic granulomatous disease. Clinical Immunology, 137(1):1-4.

Abstract

Chronic granulomatous disease (CGD) is characterized by a disability to produce reactive oxygen intermediates (ROI) caused by a defect of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. A hyperinflammatory response to immune activation has been reported to contribute to the pathology of CGD. The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is considered critical for regulating immune responses and suppression of inflammation. IDO is generally believed to require ROI for enzymatic activity and was found to be inactive in murine CGD. Here, we report that, strikingly, in human CGD IDO metabolic activity is intact. Monocyte-derived dendritic cells generated from CGD patients, harbouring X-linked and autosomal recessive forms of CGD, and from healthy controls produced similar amounts of the tryptophan metabolite kynurenine upon activation with lipopolysaccharide and interferon-γ. Thus, in humans, ROI apparently are dispensable for IDO activity. Hyperinflammation in human CGD cannot be attributed to disabled IDO activation.

Abstract

Chronic granulomatous disease (CGD) is characterized by a disability to produce reactive oxygen intermediates (ROI) caused by a defect of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. A hyperinflammatory response to immune activation has been reported to contribute to the pathology of CGD. The tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is considered critical for regulating immune responses and suppression of inflammation. IDO is generally believed to require ROI for enzymatic activity and was found to be inactive in murine CGD. Here, we report that, strikingly, in human CGD IDO metabolic activity is intact. Monocyte-derived dendritic cells generated from CGD patients, harbouring X-linked and autosomal recessive forms of CGD, and from healthy controls produced similar amounts of the tryptophan metabolite kynurenine upon activation with lipopolysaccharide and interferon-γ. Thus, in humans, ROI apparently are dispensable for IDO activity. Hyperinflammation in human CGD cannot be attributed to disabled IDO activation.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:22 Jan 2011 09:12
Last Modified:07 Dec 2017 05:29
Publisher:Elsevier
ISSN:1521-6616
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.clim.2010.05.007
PubMed ID:20570568

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