Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation

► Soluble products of T. suis and T. spiralis suppress clinical signs in murine EAE. ► Soluble products of T. suis, T. spiralis and S. mansoni modulate human dendritic cell function. ► Soluble products of T. suis and S. mansoni enhance dendritic cell OX40L expression. ► Soluble products of helminths...

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Veröffentlicht in:Molecular immunology 2012-06, Vol.51 (2), p.210-218
Hauptverfasser: Kuijk, Loes M., Klaver, Elsenoor J., Kooij, Gijs, van der Pol, Susanne M.A., Heijnen, Priscilla, Bruijns, Sven C.M., Kringel, Helene, Pinelli, Elena, Kraal, Georg, de Vries, Helga E., Dijkstra, Christine D., Bouma, Gerd, van Die, Irma
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container_end_page 218
container_issue 2
container_start_page 210
container_title Molecular immunology
container_volume 51
creator Kuijk, Loes M.
Klaver, Elsenoor J.
Kooij, Gijs
van der Pol, Susanne M.A.
Heijnen, Priscilla
Bruijns, Sven C.M.
Kringel, Helene
Pinelli, Elena
Kraal, Georg
de Vries, Helga E.
Dijkstra, Christine D.
Bouma, Gerd
van Die, Irma
description ► Soluble products of T. suis and T. spiralis suppress clinical signs in murine EAE. ► Soluble products of T. suis, T. spiralis and S. mansoni modulate human dendritic cell function. ► Soluble products of T. suis and S. mansoni enhance dendritic cell OX40L expression. ► Soluble products of helminths differentially suppress dendritic cell cytokine production. ► Dendritic cells primed with helminth soluble products suppress IL-17A secretion. 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.
doi_str_mv 10.1016/j.molimm.2012.03.020
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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. 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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. 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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.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>22482518</pmid><doi>10.1016/j.molimm.2012.03.020</doi><tpages>9</tpages></addata></record>
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subjects Animal models
Animals
Autoimmune diseases
Cell activation
Coculture Techniques
Cytokines
Data processing
Dendritic cell
Dendritic cells
Dendritic Cells - immunology
Eggs
Encephalomyelitis, Autoimmune, Experimental - immunology
Enzyme-Linked Immunosorbent Assay
Experimental allergic encephalomyelitis
Experimental autoimmune encephalomyelitis
Female
Flow Cytometry
Helminth
Helminth Proteins - immunology
Helper cells
Humans
Immune system
Immunomodulation
Immunomodulation - immunology
Infection
Inflammation
Inflammatory bowel diseases
Innate immunity
Interleukin 12
Lymphocyte Activation - immunology
Lymphocytes T
Mice
Mice, Inbred C57BL
Multiple sclerosis
Nematoda
OX40L protein
Parasites
Schistosoma mansoni
Trichinella spiralis
Tumor necrosis factor- alpha
title Soluble helminth products suppress clinical signs in murine experimental autoimmune encephalomyelitis and differentially modulate human dendritic cell activation
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