Excreted/secreted Trichuris suis products reduce barrier function and suppress inflammatory cytokine production of intestinal epithelial cells.
The administration of helminths is considered a promising strategy for the treatment of autoimmune diseases due to their immunomodulatory properties. Currently, the application of the helminth Trichuris suis as a treatment for Crohn's disease is being studied in large multi-center clinical trials. The intestinal epithelium forms an efficient barrier between the intestinal lumen containing the microbial flora and helminths, and dendritic cells (DCs) present in the lamina propria that determine the TH response. Here, we investigated how excreted/secreted (E/S) products of T. suis affect the barrier function of intestinal epithelial cells (IECs) in order to reach the DCs and modulate the immune response. We show that T. suis E/S products reduce the barrier function and the expression of the tight junction proteins EMP-1 and claudin-4 in IEC CMT93/69 monolayers in a glycan-dependent manner. This resulted in an increased passage of soluble compounds to the basolateral side that affected DC function. In addition, T. suis E/S suppressed LPS-induced pro-inflammatory cytokine production by CMT93/69 cells, whereas the production of the TH2 response-inducing cytokine thymic stromal lymphopoietin (TSLP) was induced. Our studies indicate that T. suis E/S glycans affect the function of the intestinal epithelium in order to modulate DC function. Identification of the T. suis E/S glycans that modulate IEC and DC function may lead to a strategy to reduce symptoms of autoimmune and allergic immune diseases by orally administrated helminth-derived factors without the need of infection with live helminths.
['Hiemstra|I H|IH|', 'Klaver|E J|EJ|', 'Vrijland|K|K|', 'Kringel|H|H|', 'Andreasen|A|A|', 'Bouma|G|G|', 'Kraal|G|G|', 'van Die|I|I|', 'den Haan|J M M|JM|']
D000818:Animals D001692:Biological Transport D002460:Cell Line D054360:Chemokine CXCL1 D062506:Claudin-4 D003424:Crohn Disease D016207:Cytokines D003713:Dendritic Cells D015801:Helminth Proteins D006801:Humans D007413:Intestinal Mucosa D008070:Lipopolysaccharides D051379:Mice D009363:Neoplasm Proteins D011134:Polysaccharides D011956:Receptors, Cell Surface D018418:Th2 Cells D061147:Therapy with Helminths D019108:Tight Junctions D014258:Trichuris D014409:Tumor Necrosis Factor-alpha
Trichuris suis Barrier function Intestinal epithelial cells Immune therapy