Trichuris suis soluble products induce Rab7b expression and limit TLR4 responses in human dendritic cells
Inflammatory immune disorders such as inflammatory bowel disease and multiple sclerosis are major health problems. Currently, the intestinal whipworm Trichuris suis is being explored in clinical trials to reduce inflammation in these diseases; however, the mechanisms by which the parasite affects th...
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| Veröffentlicht in: | Genes and immunity 2015-09, Vol.16 (6), p.378-387 |
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| creator | Klaver, E J van der Pouw Kraan, T C T M Laan, L C Kringel, H Cummings, R D Bouma, G Kraal, G van Die, I |
| description | Inflammatory immune disorders such as inflammatory bowel disease and multiple sclerosis are major health problems. Currently, the intestinal whipworm
Trichuris suis
is being explored in clinical trials to reduce inflammation in these diseases; however, the mechanisms by which the parasite affects the host immune system are not known. Here we determined the effects of
T. suis
soluble products (SPs) on Toll-like receptor-4 (TLR4)-stimulated human dendritic cells (DCs) using Illumina bead chip gene arrays. Pathway analysis of lipopolysaccharide-stimulated DCs with or without
T. suis
treatment showed that co-stimulation with
T. suis
SPs resulted in a downregulation of both the myeloid differentiation primary response gene 88-dependent and the TIR-domain-containing adaptor-inducing interferon-β-dependent signalling pathways triggered by TLR4. These data were verified using quantitative real-time PCR of several key genes within these pathways and/or defining their protein levels. In addition,
T. suis
SPs induce Rab7b, a negative regulator of TLR4 signalling that interferes with its trafficking, which coincided with a reduced surface expression of TLR4. These data indicate that the mechanism by which
T. suis
SPs reduce inflammatory responses is through suppression of both TLR4 signalling and surface expression on DCs. |
| doi_str_mv | 10.1038/gene.2015.18 |
| format | Article |
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Trichuris suis
is being explored in clinical trials to reduce inflammation in these diseases; however, the mechanisms by which the parasite affects the host immune system are not known. Here we determined the effects of
T. suis
soluble products (SPs) on Toll-like receptor-4 (TLR4)-stimulated human dendritic cells (DCs) using Illumina bead chip gene arrays. Pathway analysis of lipopolysaccharide-stimulated DCs with or without
T. suis
treatment showed that co-stimulation with
T. suis
SPs resulted in a downregulation of both the myeloid differentiation primary response gene 88-dependent and the TIR-domain-containing adaptor-inducing interferon-β-dependent signalling pathways triggered by TLR4. These data were verified using quantitative real-time PCR of several key genes within these pathways and/or defining their protein levels. In addition,
T. suis
SPs induce Rab7b, a negative regulator of TLR4 signalling that interferes with its trafficking, which coincided with a reduced surface expression of TLR4. These data indicate that the mechanism by which
T. suis
SPs reduce inflammatory responses is through suppression of both TLR4 signalling and surface expression on DCs.</description><identifier>ISSN: 1466-4879</identifier><identifier>EISSN: 1476-5470</identifier><identifier>DOI: 10.1038/gene.2015.18</identifier><identifier>PMID: 25996526</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38 ; 38/61 ; 38/77 ; 631/250 ; 631/250/2502/248 ; Animals ; Biological response modifiers ; Biomedicine ; Cancer Research ; Clinical trials ; Dendritic cells ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Dendritic Cells - parasitology ; DNA microarrays ; Down-Regulation ; Gene Expression ; Genetic aspects ; Health aspects ; Human Genetics ; Humans ; Immune system ; Immunology ; Inflammation ; Inflammation - immunology ; Inflammation - parasitology ; Inflammation - therapy ; Inflammatory bowel diseases ; Inflammatory diseases ; Interferon ; Intestine ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Mitogens ; Multiple sclerosis ; original-article ; rab GTP-Binding Proteins - metabolism ; Real-Time Polymerase Chain Reaction ; Risk factors ; Roundworm infections ; Signal Transduction ; TLR4 protein ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; Transcriptome ; Trichuris - immunology ; Trichuris suis ; β-Interferon</subject><ispartof>Genes and immunity, 2015-09, Vol.16 (6), p.378-387</ispartof><rights>Macmillan Publishers Limited 2015</rights><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2015</rights><rights>Macmillan Publishers Limited 2015.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c716t-c6aee65597ed228cc80004e9be063ae5fb03be5ff36542835b33f41c33a53ce93</citedby><cites>FETCH-LOGICAL-c716t-c6aee65597ed228cc80004e9be063ae5fb03be5ff36542835b33f41c33a53ce93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/gene.2015.18$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/gene.2015.18$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25996526$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Klaver, E J</creatorcontrib><creatorcontrib>van der Pouw Kraan, T C T M</creatorcontrib><creatorcontrib>Laan, L C</creatorcontrib><creatorcontrib>Kringel, H</creatorcontrib><creatorcontrib>Cummings, R D</creatorcontrib><creatorcontrib>Bouma, G</creatorcontrib><creatorcontrib>Kraal, G</creatorcontrib><creatorcontrib>van Die, I</creatorcontrib><title>Trichuris suis soluble products induce Rab7b expression and limit TLR4 responses in human dendritic cells</title><title>Genes and immunity</title><addtitle>Genes Immun</addtitle><addtitle>Genes Immun</addtitle><description>Inflammatory immune disorders such as inflammatory bowel disease and multiple sclerosis are major health problems. Currently, the intestinal whipworm
Trichuris suis
is being explored in clinical trials to reduce inflammation in these diseases; however, the mechanisms by which the parasite affects the host immune system are not known. Here we determined the effects of
T. suis
soluble products (SPs) on Toll-like receptor-4 (TLR4)-stimulated human dendritic cells (DCs) using Illumina bead chip gene arrays. Pathway analysis of lipopolysaccharide-stimulated DCs with or without
T. suis
treatment showed that co-stimulation with
T. suis
SPs resulted in a downregulation of both the myeloid differentiation primary response gene 88-dependent and the TIR-domain-containing adaptor-inducing interferon-β-dependent signalling pathways triggered by TLR4. These data were verified using quantitative real-time PCR of several key genes within these pathways and/or defining their protein levels. In addition,
T. suis
SPs induce Rab7b, a negative regulator of TLR4 signalling that interferes with its trafficking, which coincided with a reduced surface expression of TLR4. These data indicate that the mechanism by which
T. suis
SPs reduce inflammatory responses is through suppression of both TLR4 signalling and surface expression on DCs.</description><subject>38</subject><subject>38/61</subject><subject>38/77</subject><subject>631/250</subject><subject>631/250/2502/248</subject><subject>Animals</subject><subject>Biological response modifiers</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Clinical trials</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Dendritic Cells - parasitology</subject><subject>DNA microarrays</subject><subject>Down-Regulation</subject><subject>Gene Expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Inflammation - immunology</subject><subject>Inflammation - 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metabolism</topic><topic>Toll-like receptors</topic><topic>Transcriptome</topic><topic>Trichuris - immunology</topic><topic>Trichuris suis</topic><topic>β-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Klaver, E J</creatorcontrib><creatorcontrib>van der Pouw Kraan, T C T M</creatorcontrib><creatorcontrib>Laan, L C</creatorcontrib><creatorcontrib>Kringel, H</creatorcontrib><creatorcontrib>Cummings, R D</creatorcontrib><creatorcontrib>Bouma, G</creatorcontrib><creatorcontrib>Kraal, G</creatorcontrib><creatorcontrib>van Die, I</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale in Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Genes and immunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Klaver, E J</au><au>van der Pouw Kraan, T C T M</au><au>Laan, L C</au><au>Kringel, H</au><au>Cummings, R D</au><au>Bouma, G</au><au>Kraal, G</au><au>van Die, I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Trichuris suis soluble products induce Rab7b expression and limit TLR4 responses in human dendritic cells</atitle><jtitle>Genes and immunity</jtitle><stitle>Genes Immun</stitle><addtitle>Genes Immun</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>16</volume><issue>6</issue><spage>378</spage><epage>387</epage><pages>378-387</pages><issn>1466-4879</issn><eissn>1476-5470</eissn><abstract>Inflammatory immune disorders such as inflammatory bowel disease and multiple sclerosis are major health problems. Currently, the intestinal whipworm
Trichuris suis
is being explored in clinical trials to reduce inflammation in these diseases; however, the mechanisms by which the parasite affects the host immune system are not known. Here we determined the effects of
T. suis
soluble products (SPs) on Toll-like receptor-4 (TLR4)-stimulated human dendritic cells (DCs) using Illumina bead chip gene arrays. Pathway analysis of lipopolysaccharide-stimulated DCs with or without
T. suis
treatment showed that co-stimulation with
T. suis
SPs resulted in a downregulation of both the myeloid differentiation primary response gene 88-dependent and the TIR-domain-containing adaptor-inducing interferon-β-dependent signalling pathways triggered by TLR4. These data were verified using quantitative real-time PCR of several key genes within these pathways and/or defining their protein levels. In addition,
T. suis
SPs induce Rab7b, a negative regulator of TLR4 signalling that interferes with its trafficking, which coincided with a reduced surface expression of TLR4. These data indicate that the mechanism by which
T. suis
SPs reduce inflammatory responses is through suppression of both TLR4 signalling and surface expression on DCs.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>25996526</pmid><doi>10.1038/gene.2015.18</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Genes and immunity, 2015-09, Vol.16 (6), p.378-387 |
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| subjects | 38 38/61 38/77 631/250 631/250/2502/248 Animals Biological response modifiers Biomedicine Cancer Research Clinical trials Dendritic cells Dendritic Cells - drug effects Dendritic Cells - immunology Dendritic Cells - metabolism Dendritic Cells - parasitology DNA microarrays Down-Regulation Gene Expression Genetic aspects Health aspects Human Genetics Humans Immune system Immunology Inflammation Inflammation - immunology Inflammation - parasitology Inflammation - therapy Inflammatory bowel diseases Inflammatory diseases Interferon Intestine Lipopolysaccharides Lipopolysaccharides - pharmacology Mitogens Multiple sclerosis original-article rab GTP-Binding Proteins - metabolism Real-Time Polymerase Chain Reaction Risk factors Roundworm infections Signal Transduction TLR4 protein Toll-Like Receptor 4 - metabolism Toll-like receptors Transcriptome Trichuris - immunology Trichuris suis β-Interferon |
| title | Trichuris suis soluble products induce Rab7b expression and limit TLR4 responses in human dendritic cells |
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