Project description:To investigate the effect of Progranulin on neutrophils phagocytosis and killing of Candida albicans, we designed RNA-Seq analysis of wild-type and PGRN-/- neutrophils challenged with Candida albicans in vitro at one time point.
Project description:To investigate the effect of progranulin on macrophages phagocytosis and killing of Candida albicans, we designed RNA-Seq analysis of wild-type and PGRN-/- macrophages challenged with Candida albicans in vitro at one time point.
Project description:This SuperSeries is composed of the following subset Series: GSE13318: Expression profiling of Candida albicans and Candida dubliniensis in reconstituted human oral epithelium 30 min p.i. GSE13345: Expression profiling of Candida albicans and Candida dubliniensis in reconstituted human oral epithelium 90 min p.i. GSE13352: Comparative expression profiling in Candida albicans and Candida dubliniensis in inocula, RHE, and PCF cultures Refer to individual Series
Project description: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.
Project description:Candida albicans is the most prevalent fungal pathogen of humans, causing a variety of diseases ranging from superficial mucosal infections to deep-seated systemic infections. Mucus, the gel that coats all wet epithelial surfaces, accommodates Candida albicans as part of the regular microbiome where C. albicans resides asymptomatically in healthy humans. Through a series of in vitro experiments combined with genome-wide transcriptional profiling, we show that mucin biopolymers, the main gel-forming constituents of mucus, induce a new oval-shaped morphology in C. albicans in which a range of genes related to adhesion, filamentation, and biofilm formation are down-regulated. We also show that corresponding phenotypes are suppressed, rendering Candida incapable of forming biofilms on a range of different synthetic surfaces and human epithelial cells. Our data suggests that mucins can manipulate Candida physiology and we hypothesize that they are key regulators for retaining Candida in the host-compatible, commensal state.