title: Candida-specific interferon-gamma deficiency and toll-like receptor polymorphisms in patients with chronic mucocutaneous candidiasis.
abstract: Chronic mucocutaneous candidiasis (CMC) is a group of disorders, characterised by persistent mucocutaneous infections with Candida species. The underlying defect of CMC has not been elucidated, but a defective cytokine response may be involved. Therefore, we investigated whether an imbalance between IFNgamma and IL-10 may play a role in this disorder. We assessed the cytokine production in whole-blood cultures from CMC patients using Candida albicans, lipopolysaccharide and phytohaemagglutinin as stimuli. As the Toll-like receptors are important pattern recognition receptors for Candida species, we also investigated Toll-like receptor polymorphisms in these patients. Patients with CMC had a significantly decreased IFNgamma production when whole blood was stimulated with C. albicans (232 +/- 120 vs 2279 +/- 609 pg/ml, p<0.02). When stimulated with phytohaemagglutinin, the differences were not significant (3549 +/- 1320 vs 7631 +/- 1790 pg/ml). The Candida-stimulated production of IL-10 tended to be higher in CMC patients, whereas TNF and IL-1beta production were similar in patients and controls. Stimulation with LPS showed no differences in cytokine production between patients and controls. Two out of seven patients had the TLR4 Asp299Gly polymorphism and none had the TLR2 Arg677Trp polymorphism. These data support the hypothesis that deficient IFNgamma production is involved in the pathogenesis of CMC, whereas a role for genetic polymorphisms of Toll-like receptor 2 and 4 is not obvious in these patients.
authors.affiliation: Department of Internal Medicine (541), University Medical Centre St Radboud, PO Box 9101, 6500 HB Nijmegen, the Netherlands.
authors.forename: C A A
authors.initials: CA
authors.lastname: van der Graaf
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: I P H
authors.initials: IP
authors.lastname: Drenth
authors.forename: R H
authors.initials: RH
authors.lastname: te Morsche
authors.forename: J W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
mesh_terms: D000293:Adolescent; D000328:Adult; D002176:Candida albicans / Q000276:immunology*; D002178:Candidiasis, Chronic Mucocutaneous / Q000235:genetics / Q000276:immunology*; D002648:Child; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency* / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics*; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma