C. albicans in healthy people and patients with UC
Candida albicans, as an opportunistic pathogen, exhibits aberrant changes in patients with inflammatory bowel disease and dominate the colonic mucosal immune response. However, the causative agent in Candida albicans is not clear. We found that Candida albicans in IBD patients had characteristic gene expression, and PMA1 was significantly increased, compared with that in healthy controls. We used a Crispr-Cas9-based fungal strain editing system to knock out the PMA1 gene and demonstrated the important role of PMA1 in Candida albicans-aggravating colitis. Proteomic analysis showed that PMA1 is carried by extracellular vesicles of Candida albicans. Then we found PMA1-containing EVs modulated the migration of cDC2 from the lamina propria to mesenteric lymph nodes, and induced TH17 cell differentiation during colitis. Our results showed that PMA1-containing EVs promote maturation, cytokine secretion and migration of cDC2, thus promoting TH17 differentiation. Moreover, we suggested that the CARD9 expression in DCs is required for recognition of PMA1 within EVs, CARD9 deletion in DCs abrogates cytokine secretion induction by PMA1. Metabolite sequencing analysis results showed that CARD9 can activates glycolysis in DCs. As an adaptor protein, CARD9 can combined with G3P aa2-146 domain through its CARD region. These findings reveal the specific pathogenic factor of Candida albicans–host interactions in colitis progression and highlight new diagnostic and therapeutic targets for diseases of inflammatory origin. Overall design: Comparative gene expression profiling analysis of RNA-seq data for C. albicans in healthy people and patients with UC