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Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity
Fungal infections are increasing worldwide due to the marked rise in immunodeficiencies including AIDS; however, immune responses to fungi are poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate...
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| Published in: | Nature 2006-08, Vol.442 (7103), p.651-656 |
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| Main Authors: | , , , , , , , |
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| container_end_page | 656 |
| container_issue | 7103 |
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| container_title | Nature |
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| creator | Ruland, Jürgen Gross, Olaf Gewies, Andreas Finger, Katrin Schäfer, Martin Sparwasser, Tim Peschel, Christian Förster, Irmgard |
| description | Fungal infections are increasing worldwide due to the marked rise in immunodeficiencies including AIDS; however, immune responses to fungi are poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate non-Toll-like receptors (TLRs) containing immunoreceptor tyrosine-based activation motifs (ITAMs) related to those of adaptive antigen receptors. Here we identify Card9 as a key transducer of Dectin-1 signalling. Although being dispensable for TLR/MyD88-induced responses, Card9 controls Dectin-1-mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates Bcl10-Malt1-mediated NF-kappaB activation induced by zymosan. Yet, Card9 is dispensable for antigen receptor signalling that uses Carma1 as a link to Bcl10-Malt1. Thus, our results define a novel innate immune pathway and indicate that evolutionarily distinct ITAM receptors in innate and adaptive immune cells use diverse adaptor proteins to engage selectively the conserved Bcl10-Malt1 module. |
| doi_str_mv | 10.1038/nature04926 |
| format | article |
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Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate non-Toll-like receptors (TLRs) containing immunoreceptor tyrosine-based activation motifs (ITAMs) related to those of adaptive antigen receptors. Here we identify Card9 as a key transducer of Dectin-1 signalling. Although being dispensable for TLR/MyD88-induced responses, Card9 controls Dectin-1-mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates Bcl10-Malt1-mediated NF-kappaB activation induced by zymosan. Yet, Card9 is dispensable for antigen receptor signalling that uses Carma1 as a link to Bcl10-Malt1. Thus, our results define a novel innate immune pathway and indicate that evolutionarily distinct ITAM receptors in innate and adaptive immune cells use diverse adaptor proteins to engage selectively the conserved Bcl10-Malt1 module.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/nature04926</identifier><identifier>PMID: 16862125</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>Adaptor Proteins, Signal Transducing - deficiency ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - immunology ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Antigens, Fungal - immunology ; B-Cell CLL-Lymphoma 10 Protein ; Biological and medical sciences ; Candida albicans - immunology ; CARD Signaling Adaptor Proteins ; Caspases - metabolism ; Cell physiology ; Cytokines ; Cytokines - biosynthesis ; Cytokines - immunology ; Fundamental and applied biological sciences. Psychology ; Fungal infections ; Fungi - immunology ; Immune system ; Immunity, Innate - immunology ; Intracellular Signaling Peptides and Proteins - metabolism ; Lectins, C-Type ; Lymphocyte Activation - immunology ; Membrane Proteins - metabolism ; Mice ; Molecular and cellular biology ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein ; Neoplasm Proteins - metabolism ; Nerve Tissue Proteins - metabolism ; NF-kappa B - metabolism ; Protein-Tyrosine Kinases - metabolism ; Proteins ; Signal Transduction ; Syk Kinase ; Toll-Like Receptors ; Zymosan - immunology</subject><ispartof>Nature, 2006-08, Vol.442 (7103), p.651-656</ispartof><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 10, 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c533t-1fa5d2341bc53332ad08094dde0781c9c2f6d7c12408cf9f0d87bdf6193a5a3f3</citedby><cites>FETCH-LOGICAL-c533t-1fa5d2341bc53332ad08094dde0781c9c2f6d7c12408cf9f0d87bdf6193a5a3f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,2744,27957,27958</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18002329$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16862125$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ruland, Jürgen</creatorcontrib><creatorcontrib>Gross, Olaf</creatorcontrib><creatorcontrib>Gewies, Andreas</creatorcontrib><creatorcontrib>Finger, Katrin</creatorcontrib><creatorcontrib>Schäfer, Martin</creatorcontrib><creatorcontrib>Sparwasser, Tim</creatorcontrib><creatorcontrib>Peschel, Christian</creatorcontrib><creatorcontrib>Förster, Irmgard</creatorcontrib><title>Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity</title><title>Nature</title><addtitle>Nature</addtitle><description>Fungal infections are increasing worldwide due to the marked rise in immunodeficiencies including AIDS; however, immune responses to fungi are poorly understood. Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate non-Toll-like receptors (TLRs) containing immunoreceptor tyrosine-based activation motifs (ITAMs) related to those of adaptive antigen receptors. Here we identify Card9 as a key transducer of Dectin-1 signalling. Although being dispensable for TLR/MyD88-induced responses, Card9 controls Dectin-1-mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates Bcl10-Malt1-mediated NF-kappaB activation induced by zymosan. Yet, Card9 is dispensable for antigen receptor signalling that uses Carma1 as a link to Bcl10-Malt1. 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Psychology</subject><subject>Fungal infections</subject><subject>Fungi - immunology</subject><subject>Immune system</subject><subject>Immunity, Innate - immunology</subject><subject>Intracellular Signaling Peptides and Proteins - metabolism</subject><subject>Lectins, C-Type</subject><subject>Lymphocyte Activation - immunology</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Molecular and cellular biology</subject><subject>Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein</subject><subject>Neoplasm Proteins - metabolism</subject><subject>Nerve Tissue Proteins - metabolism</subject><subject>NF-kappa B - metabolism</subject><subject>Protein-Tyrosine Kinases - metabolism</subject><subject>Proteins</subject><subject>Signal Transduction</subject><subject>Syk Kinase</subject><subject>Toll-Like Receptors</subject><subject>Zymosan - immunology</subject><issn>0028-0836</issn><issn>1476-4687</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><recordid>eNqF0tuLEzEUB-AgittdffJdRkFBZDT3y2MpXhaLwlrxcTjNJDXLTKYmM7j9701pcRdR-hQCH-fknPwQekLwG4KZfhthnJLD3FB5D80IV7LmUqv7aIYx1TXWTJ6h85yvMcaCKP4QnRGpJSVUzNCnBaTWVHaIYxq6XEEVh1ivlldVDpsIXRfiptrC-OMX7Co_pCrE0s9VEMdQ-yluoKtC308xjLtH6IGHLrvHx_MCfXv_brX4WC-_fLhczJe1FYyNNfEgWso4We_vjEKLNTa8bR1WmlhjqZetsoRyrK03HrdarVsviWEggHl2gV4e6m7T8HNyeWz6kK3rOohumHJThmdCUXkSMkGoYpSfhJQQSZhUJyExVElqTIHP_4LXw5TKQksxzAUTVIqCXh1Q2aJrQtz_grsZNzDl3Fx-vWrmRAvOtZC62Nf_t_PV98Xnf2qbhpyT8802hR7SriG42aemuZOaop8eHzute9fe2mNMCnhxBJAtdD5BtCHfOl2Sxuh-6mcHd6j-B9xt9hvUpNMz</recordid><startdate>20060810</startdate><enddate>20060810</enddate><creator>Ruland, Jürgen</creator><creator>Gross, Olaf</creator><creator>Gewies, Andreas</creator><creator>Finger, Katrin</creator><creator>Schäfer, Martin</creator><creator>Sparwasser, Tim</creator><creator>Peschel, Christian</creator><creator>Förster, Irmgard</creator><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>IQODW</scope><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>ATWCN</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7SC</scope><scope>7SP</scope><scope>7SR</scope><scope>7TB</scope><scope>7U5</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope></search><sort><creationdate>20060810</creationdate><title>Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity</title><author>Ruland, Jürgen ; 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Dectin-1 is the major mammalian pattern recognition receptor for the fungal component zymosan. Dectin-1 represents the prototype of innate non-Toll-like receptors (TLRs) containing immunoreceptor tyrosine-based activation motifs (ITAMs) related to those of adaptive antigen receptors. Here we identify Card9 as a key transducer of Dectin-1 signalling. Although being dispensable for TLR/MyD88-induced responses, Card9 controls Dectin-1-mediated myeloid cell activation, cytokine production and innate anti-fungal immunity. Card9 couples to Bcl10 and regulates Bcl10-Malt1-mediated NF-kappaB activation induced by zymosan. Yet, Card9 is dispensable for antigen receptor signalling that uses Carma1 as a link to Bcl10-Malt1. Thus, our results define a novel innate immune pathway and indicate that evolutionarily distinct ITAM receptors in innate and adaptive immune cells use diverse adaptor proteins to engage selectively the conserved Bcl10-Malt1 module.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>16862125</pmid><doi>10.1038/nature04926</doi><tpages>6</tpages></addata></record> |
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| ispartof | Nature, 2006-08, Vol.442 (7103), p.651-656 |
| issn | 0028-0836 1476-4687 1476-4679 |
| language | eng |
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| source | Springer Nature - Connect here FIRST to enable access |
| subjects | Adaptor Proteins, Signal Transducing - deficiency Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - immunology Adaptor Proteins, Signal Transducing - metabolism Animals Antigens, Fungal - immunology B-Cell CLL-Lymphoma 10 Protein Biological and medical sciences Candida albicans - immunology CARD Signaling Adaptor Proteins Caspases - metabolism Cell physiology Cytokines Cytokines - biosynthesis Cytokines - immunology Fundamental and applied biological sciences. Psychology Fungal infections Fungi - immunology Immune system Immunity, Innate - immunology Intracellular Signaling Peptides and Proteins - metabolism Lectins, C-Type Lymphocyte Activation - immunology Membrane Proteins - metabolism Mice Molecular and cellular biology Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein Neoplasm Proteins - metabolism Nerve Tissue Proteins - metabolism NF-kappa B - metabolism Protein-Tyrosine Kinases - metabolism Proteins Signal Transduction Syk Kinase Toll-Like Receptors Zymosan - immunology |
| title | Card9 controls a non-TLR signalling pathway for innate anti-fungal immunity |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-09-21T23%3A01%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Card9%20controls%20a%20non-TLR%20signalling%20pathway%20for%20innate%20anti-fungal%20immunity&rft.jtitle=Nature&rft.au=Ruland,%20J%C3%BCrgen&rft.date=2006-08-10&rft.volume=442&rft.issue=7103&rft.spage=651&rft.epage=656&rft.pages=651-656&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/nature04926&rft_dat=%3Cgale_proqu%3EA185448568%3C/gale_proqu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c533t-1fa5d2341bc53332ad08094dde0781c9c2f6d7c12408cf9f0d87bdf6193a5a3f3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=204535265&rft_id=info:pmid/16862125&rft_galeid=A185448568&rfr_iscdi=true |