Tryptophan catabolism is unaffected in chronic granulomatous disease

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Abstract

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).

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Figure 1: Phagocyte NADPH oxidase activity is not required for IDO1 activity in inflammation.

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G.J.M. designed and carried out most experiments. S.W. and R.H. designed and carried out studies involving A. fumigatus. B.W. carried out initial cellular studies and B.H.C. was responsible for studies involving CGD patients. R.S. conceived the study and wrote the manuscript with G.J.M. All authors read and contributed to the final version of the manuscript.

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Correspondence to Roland Stocker.

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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

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