Aberrant type 1 immunity drives mucosal fungal infection susceptibility

The objective of this study was to understand the impact of autoimmune regulator (AIRE) on immunity against oral Candida albicans infection. Previous work indicated that autoantibodies against IL-17 and IL-22 may contribute to host susceptibility; however, there is not a 100% correlation between autoantibodies and mucosal candidiasis in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) patients, indicating that other pathways may be affected. Using a mouse model that very closely mimics what is seen in APECED patients, oral epithelial cells were sorted and RNA extracted from them to perform RNA-seq analysis to determine what other pathways may be involved. These data show that the type II interferon pathway is highly upregulated in Aire-deficient mice, while the IL-17R pathway is intact. Mouse: RNA-seq of sorted tongue epithelial cells from Aire WT and deficient mice during mucosal Candida albicans infection. For this study, oral epithelial cells (Live CD45- CD31- CD102- EpCAM+) were sorted with a FACS Aria cell sorter (>95% purity) and RNA extracted from 3 Aire WT and 3 Aire-deficient mice that had been orally infected with Candida albicans one day prior to the study. Human: RNA-seq of oral mucosal tissue from healthy donors and APECED patients. For this study, oral mucosal gingival biopsies were obtained from 4 uninfected healthy donors and 5 uninfected APECED patients and RNA extracted for RNA-seq analysis.