Hpb Regulates Epithelial Cellular Junctions

Introduction. Enteric helminths are a unique example of highly invasive yet truly tolerable parasites, promoting mechanisms of host defense favoring tissue adaptation and repair over parasite expulsion. These intestinal worms form intimate connections with the intestinal epithelium, a frontline effector of barrier immunity and integrity. Indeed, there are many commonalities between the host immune response to helminth infections and immune activation following tissue damage. However, whether helminths directly promote tissue and barrier integrity – by targeting the epithelium – to enable their persistence in the intestine remains an open question in the field.

Cellular junctions, including tight and gap junctions, are critical components of the intestinal epithelial barrier. Changes in the expression or spatial localization of tight junction components, such as Claudins (Cldn) and Cadherins (Cdh), are known to affect the integrity and permeability of the intestinal barrier.

Methods. In this work, we analyzed the expression of several tight and gap junction genes as well as integrins, extracellular matrix-scaffolding and cytoskeleton-scaffolding components both in vivo and ex vivo in organoid cultures.

Results. Our results identify changes in the expression of many genes related to epithelial junction organization and wound repair in Heligmosomoides polygyrus bakeri (Hpb)-stimulated organoids. In addition, we establish changes in the expression of the tight junction genes Cldn-4, Cldn-23 and Cdh-1 in duodenal tissues at the luminal stage of Hpb infection.

Conclusions. This work establishes that Hpb regulates the cellular connectivity of the intestinal epithelium and suggests that helminths may regulate epithelial permeability as well as epithelial wound repair.