Schistosoma mansoni Soluble Egg Antigens Induce Expression of the Negative Regulators SOCS1 and SHP1 in Human Dendritic Cells via Interaction with the Mannose Receptor

Schistosomiasis is a common debilitating human parasitic disease in (sub)tropical areas, however, schistosome infections can also protect against a variety of inflammatory diseases. This has raised broad interest in the mechanisms by which Schistosoma modulate the immune system into an anti-inflamma...

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Veröffentlicht in:PloS one 2015-04, Vol.10 (4), p.e0124089-e0124089
Hauptverfasser: Klaver, Elsenoor J, Kuijk, Loes M, Lindhorst, Thisbe K, Cummings, Richard D, van Die, Irma
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creator Klaver, Elsenoor J
Kuijk, Loes M
Lindhorst, Thisbe K
Cummings, Richard D
van Die, Irma
description Schistosomiasis is a common debilitating human parasitic disease in (sub)tropical areas, however, schistosome infections can also protect against a variety of inflammatory diseases. This has raised broad interest in the mechanisms by which Schistosoma modulate the immune system into an anti-inflammatory and regulatory state. Human dendritic cells (DCs) show many phenotypic changes upon contact with Schistosoma mansoni soluble egg antigens (SEA). We here show that oxidation of SEA glycans, but not heat-denaturation, abrogates the capacity of SEA to suppress both LPS-induced cytokine secretion and DC proliferation, indicating an important role of SEA glycans in these processes. Remarkably, interaction of SEA glycans with DCs results in a strongly increased expression of Suppressor Of Cytokine Signalling1 (SOCS1) and SH2-containing protein tyrosine Phosphatase-1 (SHP1), important negative regulators of TLR4 signalling. In addition, SEA induces the secretion of transforming growth factor β (TGF-β), and the surface expression of the costimulatory molecules Programmed Death Ligand-1 (PD-L1) and OX40 ligand (OX40L), which are known phenotypic markers for the capacity of DCs to polarize naïve T cells into Th2/Treg cell subsets. Inhibition of mannose receptor (MR)-mediated internalization of SEA into DCs by blocking with allyl α-D-mannoside or anti-MR antibodies, significantly reduced SOCS1 and SHP1 expression. In conclusion, we demonstrate that SEA glycans are essential for induction of enhanced SOCS1 and SHP1 levels in DCs via the MR. Our data provide novel mechanistic evidence for the potential of S. mansoni SEA glycans to modulate human DCs, which may contribute to the capacity of SEA to down-regulate inflammatory responses.
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This has raised broad interest in the mechanisms by which Schistosoma modulate the immune system into an anti-inflammatory and regulatory state. Human dendritic cells (DCs) show many phenotypic changes upon contact with Schistosoma mansoni soluble egg antigens (SEA). We here show that oxidation of SEA glycans, but not heat-denaturation, abrogates the capacity of SEA to suppress both LPS-induced cytokine secretion and DC proliferation, indicating an important role of SEA glycans in these processes. Remarkably, interaction of SEA glycans with DCs results in a strongly increased expression of Suppressor Of Cytokine Signalling1 (SOCS1) and SH2-containing protein tyrosine Phosphatase-1 (SHP1), important negative regulators of TLR4 signalling. In addition, SEA induces the secretion of transforming growth factor β (TGF-β), and the surface expression of the costimulatory molecules Programmed Death Ligand-1 (PD-L1) and OX40 ligand (OX40L), which are known phenotypic markers for the capacity of DCs to polarize naïve T cells into Th2/Treg cell subsets. Inhibition of mannose receptor (MR)-mediated internalization of SEA into DCs by blocking with allyl α-D-mannoside or anti-MR antibodies, significantly reduced SOCS1 and SHP1 expression. In conclusion, we demonstrate that SEA glycans are essential for induction of enhanced SOCS1 and SHP1 levels in DCs via the MR. 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This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Klaver et al 2015 Klaver et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-22863a61158b89f3f251eab65d9e13ed23fa842245fc09b8ed041eb7b758afd83</citedby><cites>FETCH-LOGICAL-c692t-22863a61158b89f3f251eab65d9e13ed23fa842245fc09b8ed041eb7b758afd83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405200/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405200/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,2915,23847,27905,27906,53772,53774,79349,79350</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25897665$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gobert, Geoffrey N.</contributor><creatorcontrib>Klaver, Elsenoor J</creatorcontrib><creatorcontrib>Kuijk, Loes M</creatorcontrib><creatorcontrib>Lindhorst, Thisbe K</creatorcontrib><creatorcontrib>Cummings, Richard D</creatorcontrib><creatorcontrib>van Die, Irma</creatorcontrib><title>Schistosoma mansoni Soluble Egg Antigens Induce Expression of the Negative Regulators SOCS1 and SHP1 in Human Dendritic Cells via Interaction with the Mannose Receptor</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Schistosomiasis is a common debilitating human parasitic disease in (sub)tropical areas, however, schistosome infections can also protect against a variety of inflammatory diseases. This has raised broad interest in the mechanisms by which Schistosoma modulate the immune system into an anti-inflammatory and regulatory state. Human dendritic cells (DCs) show many phenotypic changes upon contact with Schistosoma mansoni soluble egg antigens (SEA). We here show that oxidation of SEA glycans, but not heat-denaturation, abrogates the capacity of SEA to suppress both LPS-induced cytokine secretion and DC proliferation, indicating an important role of SEA glycans in these processes. Remarkably, interaction of SEA glycans with DCs results in a strongly increased expression of Suppressor Of Cytokine Signalling1 (SOCS1) and SH2-containing protein tyrosine Phosphatase-1 (SHP1), important negative regulators of TLR4 signalling. 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klaver, Elsenoor J</au><au>Kuijk, Loes M</au><au>Lindhorst, Thisbe K</au><au>Cummings, Richard D</au><au>van Die, Irma</au><au>Gobert, Geoffrey N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Schistosoma mansoni Soluble Egg Antigens Induce Expression of the Negative Regulators SOCS1 and SHP1 in Human Dendritic Cells via Interaction with the Mannose Receptor</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-04-21</date><risdate>2015</risdate><volume>10</volume><issue>4</issue><spage>e0124089</spage><epage>e0124089</epage><pages>e0124089-e0124089</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Schistosomiasis is a common debilitating human parasitic disease in (sub)tropical areas, however, schistosome infections can also protect against a variety of inflammatory diseases. This has raised broad interest in the mechanisms by which Schistosoma modulate the immune system into an anti-inflammatory and regulatory state. Human dendritic cells (DCs) show many phenotypic changes upon contact with Schistosoma mansoni soluble egg antigens (SEA). We here show that oxidation of SEA glycans, but not heat-denaturation, abrogates the capacity of SEA to suppress both LPS-induced cytokine secretion and DC proliferation, indicating an important role of SEA glycans in these processes. Remarkably, interaction of SEA glycans with DCs results in a strongly increased expression of Suppressor Of Cytokine Signalling1 (SOCS1) and SH2-containing protein tyrosine Phosphatase-1 (SHP1), important negative regulators of TLR4 signalling. In addition, SEA induces the secretion of transforming growth factor β (TGF-β), and the surface expression of the costimulatory molecules Programmed Death Ligand-1 (PD-L1) and OX40 ligand (OX40L), which are known phenotypic markers for the capacity of DCs to polarize naïve T cells into Th2/Treg cell subsets. Inhibition of mannose receptor (MR)-mediated internalization of SEA into DCs by blocking with allyl α-D-mannoside or anti-MR antibodies, significantly reduced SOCS1 and SHP1 expression. In conclusion, we demonstrate that SEA glycans are essential for induction of enhanced SOCS1 and SHP1 levels in DCs via the MR. Our data provide novel mechanistic evidence for the potential of S. mansoni SEA glycans to modulate human DCs, which may contribute to the capacity of SEA to down-regulate inflammatory responses.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25897665</pmid><doi>10.1371/journal.pone.0124089</doi><oa>free_for_read</oa></addata></record>
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subjects Animals
Antibodies
Antigens
Antigens, Helminth - immunology
Apoptosis
B7-H1 Antigen - genetics
B7-H1 Antigen - metabolism
Biology
Bone morphogenetic proteins
Cells, Cultured
Costimulator
Cytokines
Denaturation
Dendritic cells
Dendritic Cells - metabolism
Dendritic Cells - parasitology
Disease
Down-regulation
Gene Expression
Genotype & phenotype
Health aspects
Host-Parasite Interactions
Humans
Immune system
Immunology
Infections
Inflammatory bowel disease
Inflammatory diseases
Internalization
Lectins
Lectins, C-Type - metabolism
Ligands
Lipopolysaccharides
Lipopolysaccharides - pharmacology
Lymphocytes
Lymphocytes T
Mannose
Mannose-Binding Lectins - metabolism
Monosaccharides
Multiple sclerosis
Ovum - immunology
OX40 Ligand - genetics
OX40 Ligand - metabolism
Ox40L protein
Oxidation
Parasitic diseases
PD-L1 protein
Polysaccharides
Protein denaturation
Protein Tyrosine Phosphatase, Non-Receptor Type 6 - genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism
Protein-tyrosine-phosphatase
Receptors, Cell Surface - metabolism
Regulation
Schistosoma mansoni - immunology
Schistosomiasis
SHP-1 protein
Signaling
SOCS-1 protein
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling Proteins - genetics
Suppressor of Cytokine Signaling Proteins - metabolism
T cells
TLR4 protein
Toll-like receptors
Transcriptional Activation
Transforming growth factor
Transforming growth factor-b
Transforming growth factors
Tumor necrosis factor
Tyrosine
title Schistosoma mansoni Soluble Egg Antigens Induce Expression of the Negative Regulators SOCS1 and SHP1 in Human Dendritic Cells via Interaction with the Mannose Receptor
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