Setting off the Alarms:Candida albicansElicits Pro-Inflammatory Differential Gene Expression in Intestinal Peyer’s Patches

Abstract

24Candida albicans has been associated with a number of human diseases that pertain to 25 the gastrointestinal (GI) tract. However, the details of how gut-associated lymphoid tissues 26 (GALT) such as Peyer's patches (PPs) in the small intestine play a role in immune surveillance 27 and microbial differentiation, and what mechanisms PP use to protect the mucosal barrier in 28 response to fungal organisms such as C. albicans, are still unclear. We particularly focus on PPs 29 as they are the immune sensors and inductive sites of the gut that influence inflammation and 30 tolerance. We have previously demonstrated that CD11c + phagocytes located in the sub-31 epithelial dome (SED) within PPs sample C. albicans. To gain insight on how specific cells 32within PPs sense and respond to the sampling of fungi, we gavaged mice with C. albicans strains 33 ATCC 18804 and SC5314 as well as Saccharomyces cerevisiae. We measured the differential 34 gene expression of sorted CD45 + B220 + B-cells, CD3 + T-cells, and CD11c + DCs within the first 35 24 hrs post-gavage using nanostring nCounter® technology. The results reveal that at 24 hrs, PP 36 phagocytes were the cell type that displayed differential gene expression. These phagocytes were 37 both able to sample C. albicans and able to discriminate between strains. In particular, strain 38 ATCC 18804 upregulated fungal specific pro-inflammatory genes in CD11c + phagocytes 39 pertaining to innate and adaptive immune responses. Interestingly, PP CD11c + phagocytes 40 differentially expressed genes in response to C. albicans that were important in the protection of 41 the mucosal barrier. These results highlight that the mucosal barrier not only responds to C. 42 albicans, but also aids in the protection of the host. 43 Importance 44The specific gene expression changes within PPs that send the warning signals when 45 encountering fungi, and how PPs can discriminate between innocuous S. cerevisiae or different 46 strains of C. albicans during early stages of sampling, have not been elucidated. Here we show 47 that within the first 24 hours of sampling, CD11c + phagocytes were not only important in 48 sampling, but they were the cell type that exhibited clear differential gene expression. These 49 differentially expressed genes play important dual roles in inflammation, chemotaxis, and fungal 50 specific recognition, as well as maintaining homeostasis and protection of the mucosal barrier. 51Using nanostring technology, we were also able to demonstrate that PPs can distinguish between 52 different strains of C. albicans and can "set off the alarms" when necessary. 53 54