Arising from L. Romani et al. Nature 451, 211–215 (2008); doi:10.1038/nature06471
Chronic granulomatous disease (CGD) is an inherited disorder of phagocyte function, caused by a genetic defect in NADPH oxidase (NOX2), leading to an impaired ability of leukocytes to produce superoxide ()1; CGD subjects are susceptible to chronic infections and hyper-inflammation, although the mechanisms remain unclear. Romani et al.2 reported an aberrant inflammatory response to pulmonary aspergillosis as well as sterile Aspergillus fumigatus to be mediated by a defective tryptophan catabolism to kynurenine caused by lack of in CGD mice. Kynurenine is formed by indoleamine 2,3-dioxygenase-1 (IDO1) in a reaction originally reported to depend on (ref. 3). Here we show that NOX2 deficiency does not attenuate IDO1-mediated tryptophan catabolism in human phagocytes and CGD mice with granulomas arising from an inflammatory response to Aspergillus. There is a Reply to this Brief Communications Arising by Romani, L. & Puccetti, P. Nature 514, http://dx.doi.org/10.1038/nature13845 (2014).
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Segal, B. H., Leto, T. L., Gallin, J. I., Malech, H. L. & Holland, S. M. Genetic, biochemical, and clinical features of chronic granulomatous disease. Medicine 79, 170–200 (2000)
Romani, L. et al. Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature 451, 211–215 (2008)
Hirata, F. & Hayaishi, O. Studies on indoleamine 2,3-dioxygenase. I. Superoxide anion as substrate. J. Biol. Chem. 250, 5960–5966 (1975)
Maghzal, G. J., Thomas, S. R., Hunt, N. H. & Stocker, R. Cytochrome b5, not superoxide anion radical, is a major reductant of indoleamine 2,3-dioxygenase in human cells. J. Biol. Chem. 283, 12014–12025 (2008)
Morgenstern, D. E., Gifford, M. A., Li, L. L., Doerschuk, C. M. & Dinauer, M. C. Absence of respiratory burst in X-linked chronic granulomatous disease mice leads to abnormalities in both host defense and inflammatory response to Aspergillus fumigatus. J. Exp. Med. 185, 207–218 (1997)
Hultqvist, M. et al. Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc. Natl Acad. Sci. USA 101, 12646–12651 (2004)
Sareila, O., Jaakkola, N., Olofsson, P., Kelkka, T. & Holmdahl, R. Identification of a region in p47phox/NCF1 crucial for phagocytic NADPH oxidase (NOX2) activation. J. Leukoc. Biol. 93, 427–435 (2013)
Kelkka, T. et al. Reactive oxygen species deficiency induces autoimmunity with type 1 interferon signature. Antioxid. Redox Signal. http://dx.doi.org/10.1089/ars.2013.5828 (29 July 2014)
Thomas, S. R. & Stocker, R. Redox reactions related to indoleamine 2,3-dioxygenase and tryptophan metabolism along the kynurenine pathway. Redox Rep. 4, 199–220 (1999)
De Ravin, S. S. et al. Tryptophan/kynurenine metabolism in human leukocytes is independent of superoxide and is fully maintained in chronic granulomatous disease. Blood 116, 1755–1760 (2010)
Jürgens, B., Fuchs, D., Reichenbach, J. & Heitger, A. Intact indoleamine 2,3-dioxygenase activity in human chronic granulomatous disease. Clin. Immunol. 137, 1–4 (2010)
Heeley, A. F., Heeley, M. E., Hardy, J. & Soothill, J. F. A disorder of tryptophan metabolism in chronic granulomatous disease. Arch. Dis. Child. 45, 485–490 (1970)
Hakkim, A. et al. Response: protecting against Aspergillus infection in CGD. Blood 114, 3498 (2009)
Thomas, S. R., Mohr, D. & Stocker, R. Nitric oxide inhibits indoleamine 2,3-dioxygenase activity in interferong-primed mononuclear phagocytes. J. Biol. Chem. 269, 14457–14464 (1994)
Jackson, S. H., Gallin, J. I. & Holland, S. M. The p47phox mouse knock-out model of chronic granulomatous disease. J. Exp. Med. 182, 751–758 (1995)
Stocker, R., Winterhalter, K. H. & Richter, C. Increased fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene in the phorbol myristate acetate-stimulated plasma membrane of human neutrophils. FEBS Lett. 144, 199–203 (1982)
Competing Financial Interests Declared none.
About this article
Cite this article
Maghzal, G., Winter, S., Wurzer, B. et al. Tryptophan catabolism is unaffected in chronic granulomatous disease. Nature 514, E16–E17 (2014). https://doi.org/10.1038/nature13844
Science Advances (2020)
Trends in Molecular Medicine (2019)
Distinct roles of immunoreceptor tyrosine-based motifs in immunosuppressive indoleamine 2,3-dioxygenase 1
Journal of Cellular and Molecular Medicine (2017)
Free Radical Biology and Medicine (2017)
Immunological Reviews (2016)