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

Lookup NU author(s): Professor Fai Ng, Dr Alexei von Delwig, Dr Andrew Carmichael, Dr Mario Abinun, Professor Andrew Cant, Dr Desa Lilic

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Abstract

Background: Accumulating evidence implicates T(H)17 cytokines in protection against Candida species 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 against Candida species in human subjects. Objectives: We sought to determine whether impaired T(H)17 responses underlie susceptibility to Candida species infections and whether the same defect is present in different CMC subgroups. Methods: We assessed T(H)17 responses of PBMCs to Candida and non-Candida species stimuli by measuring IL-17, IL-22, IL-21, IL-6, IL-23, and IFN-gamma 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 to Candida species. 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. Candida species-stimulated IL-22 production was impaired in all patients with CMC, whereas IL-6 and IL-23 responses were unaltered. Conclusion: An impaired T(H)17 response to Candida species, although mediated by different mechanisms, was present in all CMC subgroups studied and might be a common factor predisposing to chronic candidiasis. (J Allergy Clin Immunol 2010;126:1006-15.)


Publication metadata

Author(s): Ng WF, von Delwig A, Carmichael AJ, Arkwright PD, Abinun M, Cant AJ, Jolles S, Lilic D

Publication type: Article

Publication status: Published

Journal: Journal of Allergy and Clinical Immunology

Year: 2010

Volume: 126

Issue: 5

Pages: 1006-1015

Print publication date: 08/10/2010

ISSN (print): 0091-6749

ISSN (electronic): 1097-6825

Publisher: Mosby, Inc.

URL: http://dx.doi.org/10.1016/j.jaci.2010.08.027

DOI: 10.1016/j.jaci.2010.08.027

Notes: See also Editorial Highlights from this journal issue: Different Th-17 cytokine defects cause chronic mucocutaneous candidiasis. Journal of Allergy and Clinical Immunology, 2010, 126(5): 941.


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