Altered Immune Activation and IL-23 Signaling in Response to Candida albicans in Autoimmune Polyendocrine Syndrome Type 1

Frontiers in Immunology

Nicolas Delaleu²  Eirik Bratland³  Bergithe E. Oftedal³  Anette S. B. Wolff³  Alexander Hellesen³  Øyvind Bruserud³  Håkon Reikvam⁴ 

[1] Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway;Computational Biology Unit, Department of Informatics, University of Bergen, Bergen, Norway;Department of Clinical Science, University of Bergen, Bergen, Norway;Department of Medicine, Haukeland University Hospital, Bergen, Norway;Swiss Institute of Bioinformatics, Lausanne, Switzerland;

关键词: autoimmune polyendocrine syndrome type 1;    chronic mucocutaneous candidiasis;    monocytes;    IL-17;    IL-22;    IL-23;   

DOI  :  10.3389/fimmu.2017.01074

来源: DOAJ

【 摘 要 】

ObjectiveAutoimmune polyendocrine syndrome type 1 (APS-1) is a rare, childhood onset disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis (CMC) is one of the three major disease components and is, to date, mainly explained by the presence of neutralizing auto-antibodies against cytokines [interleukin (IL)-17A, IL-17F, and IL-22] from T helper 17 cells, which are critical for the protection against fungal infections. However, patients without current auto-antibodies also present CMC and we, therefore, hypothesized that other immune mechanisms contribute to CMC in APS-1.MethodsWhole blood was stimulated with Candida albicans (C. albicans) in a standardized assay, and immune activation was investigated by analyzing 46 secreted immune mediators. Then, peripheral blood mononuclear cells were stimulated with curdlan, a Dectin-1 agonist and IL-23 inducer, and the IL-23p19 response in monocytes was analyzed by flow cytometry.ResultsWe found an altered immune response in APS-1 patients compared with healthy controls. Patients fail to increase the essential ILs, such as IL-2, IL-17A, IL-22, and IL-23, when stimulating whole blood with C. albicans. A significantly altered IL-23p19 response was detected in patients’ monocytes upon stimulation with curdlan.ConclusionAPS-1 patients have an altered immune response to C. albicans including a dysregulation of IL-23p19 production in monocytes. This probably contributes to the selective susceptibility to CMC found in the majority of patients.

【 授权许可】

Unknown