Project 466750

The epithelial cells that line the intestine not only function in nutrient absorption, but also serve as a crucial barrier that protects against microbial infection. Within these cells, NOD-like receptors (NLRs) act as innate sentinels that respond to specific pathogen-derived molecules, as well as danger signals that indicate a breach in the cell. Among this family of NLRs, NLR family pyrin containing 1b (Nlrp1b), which is the mouse version of human NLRP1, has been traditionally studied in immune cells, and therefore, its role in the intestinal epithelium has yet to be established. Interestingly, defects in other NLRs in the intestine have been linked to various conditions such as inflammatory bowel disease and cancer, suggesting that Nlrp1b could have a link as well. The goal of our research is to characterize Nlrp1b in the intestine using murine small intestinal organoids that recapitulate the features of the intestinal barrier. Our initial data suggests that it may be functional during enteric parasite infection, but likely only in a specific subset of intestinal epithelial cells (IECs). By further investigating this innate receptor in the intestinal epithelium and defining the IECs in which it is functional, we may begin to comprehend the physiological consequences of its activation and how it relates to parasitic defense. Additionally, the insight we gain from this research will help us better understand the human NLRP1 receptor and the similar role it likely plays in the intestine.