Candida albicans Elicits Pro-Inflammatory Differential Gene Expression in Intestinal Peyer’s Patches

Abstract

Candida albicans has been associated with a number of human diseases that pertain to the gastrointestinal (GI) tract. However, the details of how gut-associated lymphoid tissues (GALT) such as Peyer's patches (PPs) in the small intestine play a role in immune surveillance and microbial differentiation, and what mechanisms PP use to protect the mucosal barrier in response to fungal organisms such as C. albicans, are still unclear. We particularly focus on PPs as they are the immune sensors and inductive sites of the gut that influence inflammation and tolerance. We have previously demonstrated that CD11c + phagocytes located in the subepithelial dome (SED) within PPs sample C. albicans. To gain insight on how specific cells within PPs sense and respond to the sampling of fungi, we gavaged mice with C. albicans strains ATCC 18804 and SC5314 as well as Saccharomyces cerevisiae. We measured the differential gene expression of sorted CD45 + B220 + B-cells, CD3 + T-cells, and CD11c + DCs within the first 24 hrs post-gavage using nanostring nCounter® technology. The results reveal that at 24 hrs, PP phagocytes were the cell type that displayed differential gene expression. These phagocytes were both able to sample C. albicans and able to discriminate between strains. In particular, strain ATCC 18804 upregulated fungal specific pro-inflammatory genes in CD11c + phagocytes pertaining to innate and adaptive immune responses. Interestingly, PP CD11c + phagocytes differentially expressed genes in response to C. albicans that were important in the protection of the mucosal barrier. These results highlight that the mucosal barrier not only responds to C. albicans, but also aids in the protection of the host. ImportanceThe specific gene expression changes within PPs that send the warning signals when encountering fungi, and how PPs can discriminate between innocuous S. cerevisiae or different