Parasitic helminths repress the canonical intestinal stem cell program

The intestinal helminth parasite Heligmosomoides polygyrus initiates infection in mice by penetrating the duodenal mucosa, where it develops while surrounded by a multicellular granulomatous infiltrate before emerging into the intestinal lumen. We examined early H. polygyrus infection to assess the epithelial response to disruption of the mucosal barrier. Unexpectedly, intestinal stem cell markers, including Lgr5 and Olfm4, were completely lost in crypts overlying larvae-associated granulomas. We sought to identify the mechanism by which the H. polygyrus granuloma represses the activity of intestinal stem cells. CD45-negative EpCAM-positive CD44-positive crypt cells were sorted from duodenum of mice infected with H. polygyrus for six days. Crypt cells from granuloma punch biopsies was compared to crypt cells from non-granuloma punch biopsies.