Intact indoleamine 2,3-dioxygenase activity in human chronic granulomatous disease.
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.
Jürgens
Birgit
B
Children's Cancer Research Institute, Zimmermannplatz 10, A-1090, Vienna, Austria. birgit.juergens@ccri.at
Fuchs
Dietmar
D
Reichenbach
Janine
J
Heitger
Andreas
A
D015703:Antigens, CD / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003713:Dendritic Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D005260:Female; D006105:Granulomatous Disease, Chronic / Q000201:enzymology*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D007737:Kynurenine / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D014364:Tryptophan / Q000378:metabolism
D015703:Antigens, CD; D006684:HLA-DR Antigens; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; D007737:Kynurenine; D007371:Interferon-gamma; D014364:Tryptophan