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Hyperinflammation in chronic granulomatous disease and anti-inflammatory role of the phagocyte NADPH oxidase

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Abstract

Chronic granulomatous disease (CGD) is an immunodeficiency caused by the lack of the superoxide-producing phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. However, CGD patients not only suffer from recurrent infections, but also present with inflammatory, non-infectious conditions. Among the latter, granulomas figure prominently, which gave the name to the disease, and colitis, which is frequent and leads to a substantial morbidity. In this paper, we systematically review the inflammatory lesions in different organs of CGD patients and compare them to observations in CGD mouse models. In addition to the more classical inflammatory lesions, CGD patients and their relatives have increased frequency of autoimmune diseases, and CGD mice are arthritis-prone. Possible mechanisms involved in CGD hyperinflammation include decreased degradation of phagocytosed material, redox-dependent termination of proinflammatory mediators and/or signaling, as well as redox-dependent cross-talk between phagocytes and lymphocytes (e.g. defective tryptophan catabolism). As a conclusion from this review, we propose the existence of ROShigh and ROSlow inflammatory responses, which are triggered as a function of the level of reactive oxygen species and have specific characteristics in terms of physiology and pathophysiology.

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Abbreviations

CGD:

Chronic granulomatous disease

ROS:

Reactive oxygen species

NADPH:

Nicotinamide adenine dinucleotide phosphate-oxidase

NOX:

NADPH oxidase

DUOX:

dual oxidase

OR:

Odds ratio

iNOS:

inducible nitric oxide synthase

MOG:

myelin oligodendrocyte glycoprotein

IQ:

intellectual quotient

SNP:

single nucleotide polymorphism

IDO:

indol 2,3 dioxidase

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Acknowledgements

The authors would like to thank Karen Bedard and Terry Kay Epperson for critical rereading of the manuscript.

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Authors and Affiliations

  1. Gastroenterology and Hepatology Unit, Department of Paediatrics, University Hospitals of Geneva, Geneva 4, Switzerland

    Michela G. Schäppi & Dominique C. Belli

  2. Department of Pathology and Immunology and Department of Genetic and Laboratory Medicine, Geneva Medical Faculty and University Hospitals, Geneva 1211, Geneva 4, Switzerland

    Michela G. Schäppi, Vincent Jaquet & Karl-Heinz Krause

  3. Department of Genetic and Laboratory Medicine, Geneva Medical Faculty and University Hospitals, Geneva 4, Switzerland

    Michela G. Schäppi, Vincent Jaquet & Karl-Heinz Krause

  4. Paediatric Gastroenterology Unit, Clinique Universitaire de Pédiatrie, 6, rue Willy-Donzé, 1211, Geneva 4, Switzerland

    Michela G. Schäppi

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  1. Michela G. Schäppi
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Schäppi, M.G., Jaquet, V., Belli, D.C. et al. Hyperinflammation in chronic granulomatous disease and anti-inflammatory role of the phagocyte NADPH oxidase. Semin Immunopathol 30, 255–271 (2008). https://doi.org/10.1007/s00281-008-0119-2

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