Intestinal helminths remain one of the most pervasive parasites of the animal kingdom by stimulating host defense pathways that prioritize tissue adaptation over parasite expulsion. Although helminths form intimate interactions with the intestinal epithelium, their ability to directly shape the fate of this barrier cell type is unknown. Here we show that infection of mice with Heligmosomoides polygyrus bakeri (Hpb) induces a fetal reprogramming of the intestinal epithelial cell niche coincident with adult parasite adherence to intestinal villi. This reprogramming event was characterized by a regenerative Hippo pathway transcriptional signature and the emergence of Clusterin-expressing ‘revival’ stem cells (revSC) previously shown to drive intestinal repair following acute injury. Furthermore, lineage tracing studies confirmed the presence of revSC-derived progeny along the villi of Hpb-colonized animals. Remarkably, intestinal organoids exposed to Hpb excretory-secretory products rapidly assumed a spheroid morphology and expressed a fetal gene battery, a phenotype associated with gut organogenesis. By contrast, interleukin-13 inhibited revSC development in vitro while deletion of type 2 cytokine signaling in vivo led to an enhanced fetal host response and increased worm fitness. Collectively, our study reveals how a helminth parasite co-opts a tissue development program to counter type 2 immune-mediated expulsion and maintain chronic infection.
This seminar will be given online via Zoom. Details in attached poster.