Loading…
TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction
TLR-mediated signaling pathways play critical roles in host defense against microbials. However, dysregulation of innate immune and inflammatory responses triggered by TLRs would result in harmful damage to the host. Using a gene-knockout mouse model, we show that tripartite motif (TRIM) 8 negativel...
Saved in:
| Published in: | The Journal of immunology (1950) 2017-09, Vol.199 (5), p.1856-1864 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | Article |
| Language: | English |
| Subjects: | |
| Citations: | Items that this one cites Items that cite this one |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| cited_by | cdi_FETCH-LOGICAL-c369t-7c6e0bd09028f5a8d445dabb991b561e3d882b46ff1d80143eb6d661d88e9c523 |
|---|---|
| cites | cdi_FETCH-LOGICAL-c369t-7c6e0bd09028f5a8d445dabb991b561e3d882b46ff1d80143eb6d661d88e9c523 |
| container_end_page | 1864 |
| container_issue | 5 |
| container_start_page | 1856 |
| container_title | The Journal of immunology (1950) |
| container_volume | 199 |
| creator | Ye, Wen Hu, Ming-Ming Lei, Cao-Qi Zhou, Qian Lin, Heng Sun, Ming-Shun Shu, Hong-Bing |
| description | TLR-mediated signaling pathways play critical roles in host defense against microbials. However, dysregulation of innate immune and inflammatory responses triggered by TLRs would result in harmful damage to the host. Using a
gene-knockout mouse model, we show that tripartite motif (TRIM) 8 negatively regulates TLR3- and TLR4-mediated innate immune and inflammatory responses. TRIM8 deficiency leads to increased polyinosinic-polycytidylic acid- and LPS-triggered induction of downstream anti-microbial genes including
,
,
, and
, evaluated serum cytokine levels, and increased susceptibility of mice to polyinosinic-polycytidylic acid- and LPS-induced inflammatory death as well as
infection-induced loss of body weight and septic shock. TRIM8 interacted with Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and mediated its K6- and K33-linked polyubiquitination, leading to disruption of the Toll/IL-1 receptor domain-containing adapter-inducing IFN-β-TANK-binding kinase-1 association. Our findings uncover an additional mechanism on the termination of TLR3/4-mediated inflammatory and innate immune responses. |
| doi_str_mv | 10.4049/jimmunol.1601647 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1924594217</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1984375741</sourcerecordid><originalsourceid>FETCH-LOGICAL-c369t-7c6e0bd09028f5a8d445dabb991b561e3d882b46ff1d80143eb6d661d88e9c523</originalsourceid><addsrcrecordid>eNpdkc1Lw0AQxRdRbK3ePUnAi5fU2Y_sbo62WC22CiWeQ5KdlNR81Gwi9L93S1sPnoYHv_dmmEfILYWxABE-boqq6uumHFMJVAp1RoY0CMCXEuQ5GQIw5lMl1YBcWbsBAAlMXJIB00ooLtSQZNFqvtTeO66TrvjBcuetcN2XSYfWixYr_ij8JZrCaePN69pNb77fiY6z26a26KU7b1I22VdRrz2XNvOjyRt1cIdtknVFU1-TizwpLd4c54h8zp6j6au_-HiZT58WfsZl2PkqkwipgRCYzoNEGyECk6RpGNI0kBS50ZqlQuY5NRqo4JhKI6UTGsMsYHxEHg6527b57tF2cVXYDMsyqbHpbUxDJoJQMKocev8P3TR9W7vrHKUFV4ES1FFwoLK2sbbFPN62RZW0u5hCvC8gPhUQHwtwlrtjcJ9WaP4Mp4_zX4WegPY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1984375741</pqid></control><display><type>article</type><title>TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction</title><source>EZB Electronic Journals Library</source><creator>Ye, Wen ; Hu, Ming-Ming ; Lei, Cao-Qi ; Zhou, Qian ; Lin, Heng ; Sun, Ming-Shun ; Shu, Hong-Bing</creator><creatorcontrib>Ye, Wen ; Hu, Ming-Ming ; Lei, Cao-Qi ; Zhou, Qian ; Lin, Heng ; Sun, Ming-Shun ; Shu, Hong-Bing</creatorcontrib><description>TLR-mediated signaling pathways play critical roles in host defense against microbials. However, dysregulation of innate immune and inflammatory responses triggered by TLRs would result in harmful damage to the host. Using a
gene-knockout mouse model, we show that tripartite motif (TRIM) 8 negatively regulates TLR3- and TLR4-mediated innate immune and inflammatory responses. TRIM8 deficiency leads to increased polyinosinic-polycytidylic acid- and LPS-triggered induction of downstream anti-microbial genes including
,
,
, and
, evaluated serum cytokine levels, and increased susceptibility of mice to polyinosinic-polycytidylic acid- and LPS-induced inflammatory death as well as
infection-induced loss of body weight and septic shock. TRIM8 interacted with Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and mediated its K6- and K33-linked polyubiquitination, leading to disruption of the Toll/IL-1 receptor domain-containing adapter-inducing IFN-β-TANK-binding kinase-1 association. Our findings uncover an additional mechanism on the termination of TLR3/4-mediated inflammatory and innate immune responses.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.1601647</identifier><identifier>PMID: 28747347</identifier><language>eng</language><publisher>United States: American Association of Immunologists</publisher><subject>Adaptor Proteins, Vesicular Transport - metabolism ; Animals ; Body weight ; Carrier Proteins - genetics ; Carrier Proteins - metabolism ; Cytokines - genetics ; Cytokines - metabolism ; HEK293 Cells ; Humans ; Immune response ; Immunity, Innate ; Inflammation ; Inflammation - immunology ; Inflammation - microbiology ; Inflammation Mediators - metabolism ; Innate immunity ; Interleukin 1 ; Interleukin 1 receptors ; Interleukin 6 ; Lipopolysaccharides ; Lipopolysaccharides - immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Tissue Proteins - genetics ; Nerve Tissue Proteins - metabolism ; Poly I-C - immunology ; Polyinosinic:polycytidylic acid ; Protein Binding ; Protein-Serine-Threonine Kinases - metabolism ; RANTES ; Rodents ; Salmonella ; Salmonella Infections - immunology ; Salmonella typhimurium - immunology ; Septic shock ; Shock, Septic - immunology ; Signal Transduction ; TLR3 protein ; TLR4 protein ; Toll-Like Receptor 3 - metabolism ; Toll-Like Receptor 4 - metabolism ; Toll-like receptors ; Tumor necrosis factor</subject><ispartof>The Journal of immunology (1950), 2017-09, Vol.199 (5), p.1856-1864</ispartof><rights>Copyright © 2017 by The American Association of Immunologists, Inc.</rights><rights>Copyright American Association of Immunologists Sep 1, 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c369t-7c6e0bd09028f5a8d445dabb991b561e3d882b46ff1d80143eb6d661d88e9c523</citedby><cites>FETCH-LOGICAL-c369t-7c6e0bd09028f5a8d445dabb991b561e3d882b46ff1d80143eb6d661d88e9c523</cites><orcidid>0000-0001-9667-7662 ; 0000-0002-6142-4697</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28747347$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ye, Wen</creatorcontrib><creatorcontrib>Hu, Ming-Ming</creatorcontrib><creatorcontrib>Lei, Cao-Qi</creatorcontrib><creatorcontrib>Zhou, Qian</creatorcontrib><creatorcontrib>Lin, Heng</creatorcontrib><creatorcontrib>Sun, Ming-Shun</creatorcontrib><creatorcontrib>Shu, Hong-Bing</creatorcontrib><title>TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>TLR-mediated signaling pathways play critical roles in host defense against microbials. However, dysregulation of innate immune and inflammatory responses triggered by TLRs would result in harmful damage to the host. Using a
gene-knockout mouse model, we show that tripartite motif (TRIM) 8 negatively regulates TLR3- and TLR4-mediated innate immune and inflammatory responses. TRIM8 deficiency leads to increased polyinosinic-polycytidylic acid- and LPS-triggered induction of downstream anti-microbial genes including
,
,
, and
, evaluated serum cytokine levels, and increased susceptibility of mice to polyinosinic-polycytidylic acid- and LPS-induced inflammatory death as well as
infection-induced loss of body weight and septic shock. TRIM8 interacted with Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and mediated its K6- and K33-linked polyubiquitination, leading to disruption of the Toll/IL-1 receptor domain-containing adapter-inducing IFN-β-TANK-binding kinase-1 association. Our findings uncover an additional mechanism on the termination of TLR3/4-mediated inflammatory and innate immune responses.</description><subject>Adaptor Proteins, Vesicular Transport - metabolism</subject><subject>Animals</subject><subject>Body weight</subject><subject>Carrier Proteins - genetics</subject><subject>Carrier Proteins - metabolism</subject><subject>Cytokines - genetics</subject><subject>Cytokines - metabolism</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunity, Innate</subject><subject>Inflammation</subject><subject>Inflammation - immunology</subject><subject>Inflammation - microbiology</subject><subject>Inflammation Mediators - metabolism</subject><subject>Innate immunity</subject><subject>Interleukin 1</subject><subject>Interleukin 1 receptors</subject><subject>Interleukin 6</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - immunology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Nerve Tissue Proteins - genetics</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>Poly I-C - immunology</subject><subject>Polyinosinic:polycytidylic acid</subject><subject>Protein Binding</subject><subject>Protein-Serine-Threonine Kinases - metabolism</subject><subject>RANTES</subject><subject>Rodents</subject><subject>Salmonella</subject><subject>Salmonella Infections - immunology</subject><subject>Salmonella typhimurium - immunology</subject><subject>Septic shock</subject><subject>Shock, Septic - immunology</subject><subject>Signal Transduction</subject><subject>TLR3 protein</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 3 - metabolism</subject><subject>Toll-Like Receptor 4 - metabolism</subject><subject>Toll-like receptors</subject><subject>Tumor necrosis factor</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpdkc1Lw0AQxRdRbK3ePUnAi5fU2Y_sbo62WC22CiWeQ5KdlNR81Gwi9L93S1sPnoYHv_dmmEfILYWxABE-boqq6uumHFMJVAp1RoY0CMCXEuQ5GQIw5lMl1YBcWbsBAAlMXJIB00ooLtSQZNFqvtTeO66TrvjBcuetcN2XSYfWixYr_ij8JZrCaePN69pNb77fiY6z26a26KU7b1I22VdRrz2XNvOjyRt1cIdtknVFU1-TizwpLd4c54h8zp6j6au_-HiZT58WfsZl2PkqkwipgRCYzoNEGyECk6RpGNI0kBS50ZqlQuY5NRqo4JhKI6UTGsMsYHxEHg6527b57tF2cVXYDMsyqbHpbUxDJoJQMKocev8P3TR9W7vrHKUFV4ES1FFwoLK2sbbFPN62RZW0u5hCvC8gPhUQHwtwlrtjcJ9WaP4Mp4_zX4WegPY</recordid><startdate>20170901</startdate><enddate>20170901</enddate><creator>Ye, Wen</creator><creator>Hu, Ming-Ming</creator><creator>Lei, Cao-Qi</creator><creator>Zhou, Qian</creator><creator>Lin, Heng</creator><creator>Sun, Ming-Shun</creator><creator>Shu, Hong-Bing</creator><general>American Association of Immunologists</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9667-7662</orcidid><orcidid>https://orcid.org/0000-0002-6142-4697</orcidid></search><sort><creationdate>20170901</creationdate><title>TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction</title><author>Ye, Wen ; Hu, Ming-Ming ; Lei, Cao-Qi ; Zhou, Qian ; Lin, Heng ; Sun, Ming-Shun ; Shu, Hong-Bing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c369t-7c6e0bd09028f5a8d445dabb991b561e3d882b46ff1d80143eb6d661d88e9c523</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adaptor Proteins, Vesicular Transport - metabolism</topic><topic>Animals</topic><topic>Body weight</topic><topic>Carrier Proteins - genetics</topic><topic>Carrier Proteins - metabolism</topic><topic>Cytokines - genetics</topic><topic>Cytokines - metabolism</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Immune response</topic><topic>Immunity, Innate</topic><topic>Inflammation</topic><topic>Inflammation - immunology</topic><topic>Inflammation - microbiology</topic><topic>Inflammation Mediators - metabolism</topic><topic>Innate immunity</topic><topic>Interleukin 1</topic><topic>Interleukin 1 receptors</topic><topic>Interleukin 6</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - immunology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Nerve Tissue Proteins - genetics</topic><topic>Nerve Tissue Proteins - metabolism</topic><topic>Poly I-C - immunology</topic><topic>Polyinosinic:polycytidylic acid</topic><topic>Protein Binding</topic><topic>Protein-Serine-Threonine Kinases - metabolism</topic><topic>RANTES</topic><topic>Rodents</topic><topic>Salmonella</topic><topic>Salmonella Infections - immunology</topic><topic>Salmonella typhimurium - immunology</topic><topic>Septic shock</topic><topic>Shock, Septic - immunology</topic><topic>Signal Transduction</topic><topic>TLR3 protein</topic><topic>TLR4 protein</topic><topic>Toll-Like Receptor 3 - metabolism</topic><topic>Toll-Like Receptor 4 - metabolism</topic><topic>Toll-like receptors</topic><topic>Tumor necrosis factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ye, Wen</creatorcontrib><creatorcontrib>Hu, Ming-Ming</creatorcontrib><creatorcontrib>Lei, Cao-Qi</creatorcontrib><creatorcontrib>Zhou, Qian</creatorcontrib><creatorcontrib>Lin, Heng</creatorcontrib><creatorcontrib>Sun, Ming-Shun</creatorcontrib><creatorcontrib>Shu, Hong-Bing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ye, Wen</au><au>Hu, Ming-Ming</au><au>Lei, Cao-Qi</au><au>Zhou, Qian</au><au>Lin, Heng</au><au>Sun, Ming-Shun</au><au>Shu, Hong-Bing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2017-09-01</date><risdate>2017</risdate><volume>199</volume><issue>5</issue><spage>1856</spage><epage>1864</epage><pages>1856-1864</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>TLR-mediated signaling pathways play critical roles in host defense against microbials. However, dysregulation of innate immune and inflammatory responses triggered by TLRs would result in harmful damage to the host. Using a
gene-knockout mouse model, we show that tripartite motif (TRIM) 8 negatively regulates TLR3- and TLR4-mediated innate immune and inflammatory responses. TRIM8 deficiency leads to increased polyinosinic-polycytidylic acid- and LPS-triggered induction of downstream anti-microbial genes including
,
,
, and
, evaluated serum cytokine levels, and increased susceptibility of mice to polyinosinic-polycytidylic acid- and LPS-induced inflammatory death as well as
infection-induced loss of body weight and septic shock. TRIM8 interacted with Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and mediated its K6- and K33-linked polyubiquitination, leading to disruption of the Toll/IL-1 receptor domain-containing adapter-inducing IFN-β-TANK-binding kinase-1 association. Our findings uncover an additional mechanism on the termination of TLR3/4-mediated inflammatory and innate immune responses.</abstract><cop>United States</cop><pub>American Association of Immunologists</pub><pmid>28747347</pmid><doi>10.4049/jimmunol.1601647</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-9667-7662</orcidid><orcidid>https://orcid.org/0000-0002-6142-4697</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-1767 |
| ispartof | The Journal of immunology (1950), 2017-09, Vol.199 (5), p.1856-1864 |
| issn | 0022-1767 1550-6606 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1924594217 |
| source | EZB Electronic Journals Library |
| subjects | Adaptor Proteins, Vesicular Transport - metabolism Animals Body weight Carrier Proteins - genetics Carrier Proteins - metabolism Cytokines - genetics Cytokines - metabolism HEK293 Cells Humans Immune response Immunity, Innate Inflammation Inflammation - immunology Inflammation - microbiology Inflammation Mediators - metabolism Innate immunity Interleukin 1 Interleukin 1 receptors Interleukin 6 Lipopolysaccharides Lipopolysaccharides - immunology Mice Mice, Inbred C57BL Mice, Knockout Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Poly I-C - immunology Polyinosinic:polycytidylic acid Protein Binding Protein-Serine-Threonine Kinases - metabolism RANTES Rodents Salmonella Salmonella Infections - immunology Salmonella typhimurium - immunology Septic shock Shock, Septic - immunology Signal Transduction TLR3 protein TLR4 protein Toll-Like Receptor 3 - metabolism Toll-Like Receptor 4 - metabolism Toll-like receptors Tumor necrosis factor |
| title | TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-22T19%3A24%3A33IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=TRIM8%20Negatively%20Regulates%20TLR3/4-Mediated%20Innate%20Immune%20Response%20by%20Blocking%20TRIF-TBK1%20Interaction&rft.jtitle=The%20Journal%20of%20immunology%20(1950)&rft.au=Ye,%20Wen&rft.date=2017-09-01&rft.volume=199&rft.issue=5&rft.spage=1856&rft.epage=1864&rft.pages=1856-1864&rft.issn=0022-1767&rft.eissn=1550-6606&rft_id=info:doi/10.4049/jimmunol.1601647&rft_dat=%3Cproquest_cross%3E1984375741%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c369t-7c6e0bd09028f5a8d445dabb991b561e3d882b46ff1d80143eb6d661d88e9c523%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1984375741&rft_id=info:pmid/28747347&rfr_iscdi=true |