Document Detail

Low Interleukin-17A Production in Response to Fungal Pathogens in Patients with Chronic Granulomatous Disease.
MedLine Citation:
PMID:  22191467     Owner:  NLM     Status:  Publisher    
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-α, and interferon-γ 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.
Sanne P Smeekens; Stefanie S V Henriet; Mark S Gresnigt; Leo A B Joosten; Peter W M Hermans; Mihai G Netea; Adilia Warris; Frank L van de Veerdonk
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-22
Journal Detail:
Title:  Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research     Volume:  -     ISSN:  1557-7465     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9507088     Medline TA:  J Interferon Cytokine Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1 Department of Medicine, Radboud University Nijmegen Medical Centre , Nijmegen, The Netherlands .
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