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Characterizing the NLRP1B Inflammasome in the Intestinal Epithelium

Mazzone, RJ;

The intestine is a non-sterile organ that must maintain its epithelial barrier to prevent microbial invasion into deeper tissue. Intestinal epithelial cells (IECs) are equipped with innate immune receptors, such as NOD-like receptors (NLRs), that facilitate destruction of infected cells and initiate an inflammatory response through inflammasome formation. NLRP1B, the major mouse homolog of human NLRP1, has been primarily studied in macrophages; and therefore, very little is known about this NLR in the intestinal epithelium. Here, we determine that NLRP1B is expressed higher in murine ileal organoids than in bone marrow-derived macrophages (BMDMs), however, only BMDMs are responsive to the NLRP1B activator, Val-boro-Pro. Additionally, IL-13, which is important in enteric parasite defense, induces Nlrp1b expression and this was confirmed in vivo using Tritrichomonas muris infection. Overall, our data suggests that the NLRP1B inflammasome is differentially regulated in IECs and BMDMs and could have a novel role in enteric parasite infection.