Intestinal Regulation of C. albicans by PP Langerin+ DCs

Abstract

Abstract As the largest mucosal compartment, the human gastrointestinal tract (GI) is highly colonized with a complex microbial ecosystem that includes fungal organisms. Although fewer in numbers and less extensively studied in the context of the intestinal mucosa, it is unclear whether commensal members such as Candida species play a role in intestinal mucosal immunity. Recent studies have suggested that Candida sp. in the intestinal mucosa are associated with a number of human diseases such as gastric ulcers, Crohn’s disease and Hirschsprung-associated enterocolitis. We have recently identified, a specific non-macrophage dendritic cell (DC) population within intestinal Peyer’s patches (PP) that expresses the C-type lectin receptor (CLR)-Langerin and are able to specifically uptake Candida albicans, Candida tropicalis and yeast purified β-1,3-glucan particles (GPs). We hypothesize that Langerin+ DCs are central in the sampling, presentation and regulation of C. albicans within PPs. To address this hypothesis, we are currently defining the role of Langerin+ DCs in the processing of Candida sp. after uptake using the Langerin-DTR- EGFP mouse model as well as the Langerin-DTR- EGFP-DSS model. We are also characterizing the local gene expression profiles of PP B and T- lymphocytes as well as Langerin+ DCs in response to C. albicans. Additionally, we are investigating whether Langerin+ DCs are a migratory cell subset that not only transports C. albicans near germinal centers but can also take them to tolerogenic sites such as the MLN. These studies will advance our knowledge of how commensal members that are also part of the “mycobiome” are sampled, what mucosal immune responses are elicited and how these fungal organisms are tolerated.