The Frenemy Within: on Helminth Regulation of the Epithelial Barrier

Introduction. The intestinal epithelium is a complex, multifunctional tissue and one of the most highly regenerative organs in the human body. It balances nutrient absorption and waste removal with immune sensing and tolerance to food and the commensal microbiota. The intestine is also the site of many inflammatory and infectious diseases, including parasitic infections. Helminths, while tissue invasive in nature, are also uniquely well tolerated by their hosts, making them the ideal model system to investigate the different mechanisms governing tissue protection. Thus, our lab uses these gut enemies to understand novel mechanisms maintaining intestinal integrity and tissue health. We have recently demonstrated that the enteric, parasitic nematode Heligmosomoides polygyrus bakeri (Hpb) directly communicate with the intestinal stem cell compartment, tuning the epithelium to a pro-regenerative fetal-like state poised for recovery following barrier damage.
Methods. In this work, we use 3D organoids cultures as well as Hpb infection models, pharmacological, biochemical and genetic interventions, transcriptomics and advanced imaging techniques to investigate how helminths regulate the intestinal epithelial barrier.
Results. We establish that Hpb regulates several layers of epithelial function including a pro-regenerative TGFβ receptor signaling in the stem cell compartment, tight-junction formation along the villus-crypt axis and epithelial wound repair.
Conclusions. Collectively our work suggest that Hpb may regulate epithelial permeability, the epithelial response to injury as well as the regenerative capacity of the intestinal stem cell compartment, highlighting the ability of helminths to promote multiple aspects of epithelial resilience.