IL-22 neutralizing autoantibodies impair fungal clearance in murine oropharyngeal candidiasis model
- PMID: 29150834
- PMCID: PMC5844855
- DOI: 10.1002/eji.201747209
IL-22 neutralizing autoantibodies impair fungal clearance in murine oropharyngeal candidiasis model
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.
Keywords: Aire; Cytokine autoantibodies; IL-22; Oropharyngeal candidiasis; Th17.
© 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Conflict of interest statement
KK and PP are co-cofounders and shareholders of ImmunoQure AG. All other authors declare no financial or commercial conflict of interest.
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