Impaired TH17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy

• Published in: Journal of allergy and clinical immunology Vol. 126; no. 5; pp. 1006 - 1015.e4
• Main Authors: Ng, Wan-Fai, von Delwig, Alexei, Carmichael, Andrew J., Arkwright, Peter D., Abinun, Mario, Cant, Andrew J., Jolles, Stephen, Lilic, Desa
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier 01.11.2010; Elsevier Limited
• Subjects: Biological and medical sciences; Cell culture; Cytokines; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Human subjects; Hypothyroidism; Immune system; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infections; Laboratories; Medical sciences; Medical treatment; Mutation; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Endocrinopathy; Autoimmunity; Skin disease; Candidiasis; Mycosis; Interleukin 22; APECED syndrome; autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy autoimmune polyendocrinopathy type 1; Candida species; IL-22; chronic mucocutaneous candidiasis; Fungi; IFN-γ; Immunology; Autoimmune polyglandular syndrome type 1; T; Primary; primary immunodeficiency; Mucocutaneous; cytokines; Fungi Imperfecti; Th17 lymphocyte; Species; Human; Immunopathology; 17; Cytokine; autoimmune regulator; Immune deficiency; Infection; Chronic; Candida; Gamma interferon
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2010.08.027

Background Accumulating evidence implicates TH17 cytokines in protection againstCandidaspecies infections, but the clinical relevance is not clear. Chronic mucocutaneous candidiasis (CMC) is a heterogeneous syndrome with the unifying feature of selective susceptibility to chronic candidiasis. Different subgroups with distinct clinical features are recognized, including autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), CMC with hypothyroidism, and isolated CMC. Understanding immune defects in patients with CMC will define cellular and molecular mechanisms crucial for protection againstCandidaspecies in human subjects. Objectives We sought to determine whether impaired TH17 responses underlie susceptibility toCandidaspecies infections and whether the same defect is present in different CMC subgroups. Methods We assessed TH17 responses of PBMCs toCandidaand non-Candidaspecies stimuli by measuring IL-17, IL-22, IL-21, IL-6, IL-23, and IFN-γ cytokine production using cytokine arrays and intracellular cytokine-producing cell numbers and proliferation with flow cytometry. PBMCs from healthy subjects and unaffected family members served as controls. Results In patients with CMC with hypothyroidism, TH17 cells demonstrated decreased proliferation and IL-17 production in response toCandidaspecies. In contrast, in patients with APECED, TH17 cell proliferation and IL-17 production were normal unless exposed to APECED plasma, which inhibited both functions in both APECED and normal PBMCs.Candidaspecies-stimulated IL-22 production was impaired in all patients with CMC, whereas IL-6 and IL-23 responses were unaltered. Conclusion An impaired TH17 response toCandidaspecies, although mediated by different mechanisms, was present in all CMC subgroups studied and might be a common factor predisposing to chronic candidiasis.