IL‐22 neutralizing autoantibodies impair fungal clearance in murine oropharyngeal candidiasis model |
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Authors: | Rudolf Bichele Jaanika Kärner Kai Truusalu Imbi Smidt Reet Mändar Heather R Conti Sarah L Gaffen Pärt Peterson Martti Laan Kai Kisand |
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Institution: | 1. Department of Molecular Pathology, Institute of Biomedical and Translational Medicine, University of Tartu, Tartu, Estonia;2. Department of Microbiology, Institute of Biomedical and Translational Medicine, University of Tartu, Tartu, Estonia;3. Division of Rheumatology and Clinical Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA;4. Department of Biological Sciences, University of Toledo, Toledo, OH, USA |
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Abstract: | Protection against mucocutaneous candidiasis depends on the T helper (Th)17 pathway, as gene defects affecting its integrity result in inability to clear Candida albicans infection on body surfaces. Moreover, autoantibodies neutralizing Th17 cytokines have been related to chronic candidiasis in a rare inherited disorder called autoimmune polyendocriopathy candidiasis ectodermal dystrophy (APECED) caused by mutations in autoimmune regulator (AIRE) gene. However, the direct pathogenicity of these autoantibodies has not yet been addressed. Here we show that the level of anti‐IL17A autoantibodies that develop in aged Aire‐deficient mice is not sufficient for conferring susceptibility to oropharyngeal candidiasis. However, patient‐derived monoclonal antibodies that cross‐react with murine IL‐22 increase the fungal burden on C. albicans infected mucosa. Nevertheless, the lack of macroscopically evident infectious pathology on the oral mucosa of infected mice suggests that additional susceptibility factors are needed to precipitate a clinical disease. |
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Keywords: | Aire Cytokine autoantibodies IL‐22 Oropharyngeal candidiasis Th17 |
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