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.
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
I H
IH
Hiemstra
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
E J
EJ
Klaver
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
K
K
Vrijland
Section for Parasitology, Health and Development Department of Veterinary Disease Biology, University of Copenhagen, Denmark.
H
H
Kringel
Section for Parasitology, Health and Development Department of Veterinary Disease Biology, University of Copenhagen, Denmark.
A
A
Andreasen
Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands.
G
G
Bouma
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
G
G
Kraal
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: im.vandie@vumc.nl.
I
I
van Die
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
J M M
JM
den Haan
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D054360:Chemokine CXCL1 / Q000096:biosynthesis; D062506:Claudin-4 / Q000096:biosynthesis; D003424:Crohn Disease / Q000628:therapy; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D015801:Helminth Proteins / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008070:Lipopolysaccharides; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011134:Polysaccharides / Q000008:administration & dosage / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D018418:Th2 Cells / Q000276:immunology; D061147:Therapy with Helminths / Q000379:methods*; D019108:Tight Junctions / Q000276:immunology; D014258:Trichuris / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000094632:Thymic Stromal Lymphopoietin
D054360:Chemokine CXCL1; D062506:Claudin-4; C568158:Cldn4 protein, mouse; C475895:Cxcl1 protein, mouse; D016207:Cytokines; D015801:Helminth Proteins; D008070:Lipopolysaccharides; D009363:Neoplasm Proteins; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; C097051:epithelial membrane protein-1; D000094632:Thymic Stromal Lymphopoietin
Barrier function; Immune therapy; Intestinal epithelial cells; Trichuris suis