Low interleukin-17A production in response to fungal pathogens in patients with chronic granulomatous disease.
SourceJournal of Interferon and Cytokine Research, 32, 4, (2012), pp. 159-168
1 april 2012
Article / Letter to editor
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Paediatrics - OUD tm 2017
Laboratory of Genetic, Endocrine and Metabolic Diseases
Journal of Interferon and Cytokine Research
SubjectN4i 1: Pathogenesis and modulation of inflammation; N4i 1: Pathogenesis and modulation of inflammation NCMLS 1: Infection and autoimmunity; N4i 2: Invasive mycoses and compromised host
Patients with chronic granulomatous disease (CGD) cannot produce reactive oxygen species (ROS) due to a genetic defect in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system. Dysregulation of the L-tryptophan metabolism in mice with defects in NADPH oxidase, resulting in overproduction of interleukin (IL)-17, has been proposed to link ROS defects with hyperinflammation and susceptibility to pulmonary aspergillosis. In this study, we assessed the L-tryptophan metabolism and cytokine profiles in response to fungal pathogens in CGD patients. Peripheral blood mononuclear cells (PBMCs) from CGD patients showed increased production of IL-6, tumor necrosis factor-alpha, and interferon-gamma upon stimulation with Aspergillus or Candida species, while IL-17A production was strikingly low compared with healthy controls. Indoleamine 2,3-dioxygenase expression was similar in PBMCs and neutrophils from CGD patients compared with healthy controls. Conversion of L-tryptophan to L-kynurenine, as measured by high-performance liquid chromatography, did not differ between CGD patients and healthy controls. Moreover, adding L-kynurenine to the cell cultures did not suppress fungal-induced IL-17A production. Although PBMCs of CGD patients produced more proinflammatory cytokines after stimulation, IL-17A production was strikingly low in response to fungal pathogens when compared with healthy controls. In addition, cells from CGD patients did not display a defective L-tryptophan metabolism.
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