title: Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation.
abstract: The increased incidence of auto-inflammatory and autoimmune diseases in the developed countries seems to be caused by an imbalance of the immune system due to the lack of proper regulation. Helminth parasites are well known modulators of the immune system and as such are of great interest for the treatment of these disorders. Clinical studies showed that administration of eggs of the pig nematode Trichuris suis to patients with inflammatory bowel disease reduces the disease severity. Here we demonstrate that treatment with soluble products from the nematodes T. suis and Trichinella spiralis induces significant suppression of symptoms in murine experimental autoimmune encephalomyelitis, a validated animal model for multiple sclerosis. These data show that infection with live nematodes is not a prerequisite for suppression of inflammation. To translate these results to the human system, the effects of soluble products of T. suis, T. spiralis and Schistosoma mansoni on the phenotype and function of human dendritic cells (DCs) were compared. Our data show that soluble products of T. suis, S. mansoni and T. spiralis suppress TNF-α and IL-12 secretion by TLR-activated human DCs, and that T. suis and S. mansoni, but not T. spiralis, strongly enhance expression of OX40L. Furthermore, helminth-primed human DCs differentially suppress the development of Th1 and/or Th17 cells. In conclusion, our data demonstrate that soluble helminth products have strong immunomodulatory capacities, but might exert their effects through different mechanisms. The suppressed secretion of pro-inflammatory cytokines together with an upregulation of OX40L expression on human DCs might contribute to achieve this modulation.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Loes M
authors.initials: LM
authors.lastname: Kuijk
authors.forename: Elsenoor J
authors.initials: EJ
authors.lastname: Klaver
authors.forename: Gijs
authors.initials: G
authors.lastname: Kooij
authors.forename: Susanne M A
authors.initials: SM
authors.lastname: van der Pol
authors.forename: Priscilla
authors.initials: P
authors.lastname: Heijnen
authors.forename: Sven C M
authors.initials: SC
authors.lastname: Bruijns
authors.forename: Helene
authors.initials: H
authors.lastname: Kringel
authors.forename: Elena
authors.initials: E
authors.lastname: Pinelli
authors.forename: Georg
authors.initials: G
authors.lastname: Kraal
authors.forename: Helga E
authors.initials: HE
authors.lastname: de Vries
authors.forename: Christine D
authors.initials: CD
authors.lastname: Dijkstra
authors.forename: Gerd
authors.initials: G
authors.lastname: Bouma
authors.forename: Irma
authors.initials: I
authors.lastname: van Die
mesh_terms: D000818:Animals; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015801:Helminth Proteins / Q000276:immunology*; D006801:Humans; D056747:Immunomodulation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D015801:Helminth Proteins