Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88
The innate immune system evolved to recognize conserved microbial products, termed pathogen-associated molecular patterns (PAMPs), which are invariant among diverse groups of microorganisms. PAMPs are recognized by a set of germ-line encoded pattern recognition receptors (PRRs). Among the best chara...
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| Veröffentlicht in: | Current biology 2000-09, Vol.10 (18), p.1139-1142 |
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| creator | Schnare, Markus Holt†, Agnieszka Czopik Takeda, Kiyoshi Akira, Shizuo Medzhitov, Ruslan |
| description | The innate immune system evolved to recognize conserved microbial products, termed pathogen-associated molecular patterns (PAMPs), which are invariant among diverse groups of microorganisms. PAMPs are recognized by a set of germ-line encoded pattern recognition receptors (PRRs). Among the best characterized PAMPs are bacterial lipopolysaccharide (LPS), peptidoglycan (PGN), mannans, and other constituents of bacterial and fungal cell walls, as well as bacterial DNA. Recognition of bacterial DNA is the most enigmatic of these, as it depends on a particular sequence motif, called the CpG motif, in which an unmethylated CpG present in a particular sequence context accounts for a potent immunostimulatory activity of CpG DNA. Receptor(s) of the innate immune system that mediate recognition of CpG DNA are currently unknown. Here, we report that recognition of CpG DNA requires MyD88, an adaptor protein involved in signal transduction by the Toll-like receptors (TLRs), essential components of innate immune recognition in both Drosophila and mammals [1,2]. Signaling induced by CpG DNA was found to be unaffected in cells deficient in TLR2 or TLR4, suggesting that some other member of the Toll family mediates recognition of bacterial DNA. |
| doi_str_mv | 10.1016/S0960-9822(00)00700-4 |
| format | Article |
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PAMPs are recognized by a set of germ-line encoded pattern recognition receptors (PRRs). Among the best characterized PAMPs are bacterial lipopolysaccharide (LPS), peptidoglycan (PGN), mannans, and other constituents of bacterial and fungal cell walls, as well as bacterial DNA. Recognition of bacterial DNA is the most enigmatic of these, as it depends on a particular sequence motif, called the CpG motif, in which an unmethylated CpG present in a particular sequence context accounts for a potent immunostimulatory activity of CpG DNA. Receptor(s) of the innate immune system that mediate recognition of CpG DNA are currently unknown. Here, we report that recognition of CpG DNA requires MyD88, an adaptor protein involved in signal transduction by the Toll-like receptors (TLRs), essential components of innate immune recognition in both Drosophila and mammals [1,2]. Signaling induced by CpG DNA was found to be unaffected in cells deficient in TLR2 or TLR4, suggesting that some other member of the Toll family mediates recognition of bacterial DNA.</description><identifier>ISSN: 0960-9822</identifier><identifier>EISSN: 1879-0445</identifier><identifier>DOI: 10.1016/S0960-9822(00)00700-4</identifier><identifier>PMID: 10996797</identifier><language>eng</language><publisher>England: Elsevier Inc</publisher><subject>Adaptor Proteins, Signal Transducing ; Animals ; Antigens, Differentiation - genetics ; Antigens, Differentiation - metabolism ; B-Lymphocytes - immunology ; B-Lymphocytes - metabolism ; CpG Islands - genetics ; CpG Islands - immunology ; Dendritic Cells - metabolism ; DNA - genetics ; DNA - metabolism ; Drosophila Proteins ; Enzyme-Linked Immunosorbent Assay ; Interleukin-6 - metabolism ; Macrophages, Peritoneal - metabolism ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Mice ; Mice, Knockout ; MyD88 protein ; Myeloid Differentiation Factor 88 ; pathogen-associated molecular patterns ; Receptors, Cell Surface - genetics ; Receptors, Cell Surface - metabolism ; Receptors, Immunologic ; Signal Transduction ; TLR2 protein ; TLR4 protein ; Toll-Like Receptor 2 ; Toll-Like Receptor 4 ; Toll-Like Receptors</subject><ispartof>Current biology, 2000-09, Vol.10 (18), p.1139-1142</ispartof><rights>2000 Elsevier Science Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c557t-fb6dd31252d38191af98b91a1dc576420541881f7080313f4ea4a5111d5753bc3</citedby><cites>FETCH-LOGICAL-c557t-fb6dd31252d38191af98b91a1dc576420541881f7080313f4ea4a5111d5753bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960982200007004$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10996797$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schnare, Markus</creatorcontrib><creatorcontrib>Holt†, Agnieszka Czopik</creatorcontrib><creatorcontrib>Takeda, Kiyoshi</creatorcontrib><creatorcontrib>Akira, Shizuo</creatorcontrib><creatorcontrib>Medzhitov, Ruslan</creatorcontrib><title>Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88</title><title>Current biology</title><addtitle>Curr Biol</addtitle><description>The innate immune system evolved to recognize conserved microbial products, termed pathogen-associated molecular patterns (PAMPs), which are invariant among diverse groups of microorganisms. 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Signaling induced by CpG DNA was found to be unaffected in cells deficient in TLR2 or TLR4, suggesting that some other member of the Toll family mediates recognition of bacterial DNA.</description><subject>Adaptor Proteins, Signal Transducing</subject><subject>Animals</subject><subject>Antigens, Differentiation - genetics</subject><subject>Antigens, Differentiation - metabolism</subject><subject>B-Lymphocytes - immunology</subject><subject>B-Lymphocytes - metabolism</subject><subject>CpG Islands - genetics</subject><subject>CpG Islands - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>DNA - genetics</subject><subject>DNA - metabolism</subject><subject>Drosophila Proteins</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Interleukin-6 - metabolism</subject><subject>Macrophages, Peritoneal - metabolism</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>MyD88 protein</subject><subject>Myeloid Differentiation Factor 88</subject><subject>pathogen-associated molecular patterns</subject><subject>Receptors, Cell Surface - genetics</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Receptors, Immunologic</subject><subject>Signal Transduction</subject><subject>TLR2 protein</subject><subject>TLR4 protein</subject><subject>Toll-Like Receptor 2</subject><subject>Toll-Like Receptor 4</subject><subject>Toll-Like Receptors</subject><issn>0960-9822</issn><issn>1879-0445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAURa0K1A6lP6HIK1QWgfeSOLZXVTWFglRA4mNtOfbL1NWMk8aeovn3uJ0Ksevqbc59VzqXsVOE9wjYffgJuoNKq7o-A3gHIAGq9oAtUEldQduKF2zxDzlir1K6BcBa6e6QHSFo3UktF8z8IDeuYshhjHwc-HK64pffLnhIfEM-2Eye9zuewiradYgrPtl888fuEvc0UfQUMy_JfEPcejvlcebTPGYKkX_dXSr1mr0c7DrRydM9Zr8_ffy1_Fxdf7_6sry4rpwQMldD33nfYC1q3yjUaAet-nLQOyG7tgbRolI4SFDQYDO0ZFsrENELKZreNcfs7f5vab_bUspmE5Kj9dpGGrfJyLqWGrF7FkTZNaq4KaDYg24eU5ppMNMcNnbeGQTzMIF5nMA8-DUA5nEC05bcm6eCbV8U_pfaOy_A-R6g4uM-0GySCxRd0T2Ty8aP4ZmKv9itlCQ</recordid><startdate>20000921</startdate><enddate>20000921</enddate><creator>Schnare, Markus</creator><creator>Holt†, Agnieszka Czopik</creator><creator>Takeda, Kiyoshi</creator><creator>Akira, Shizuo</creator><creator>Medzhitov, Ruslan</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20000921</creationdate><title>Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88</title><author>Schnare, Markus ; Holt†, Agnieszka Czopik ; Takeda, Kiyoshi ; Akira, Shizuo ; Medzhitov, Ruslan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c557t-fb6dd31252d38191af98b91a1dc576420541881f7080313f4ea4a5111d5753bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Adaptor Proteins, Signal Transducing</topic><topic>Animals</topic><topic>Antigens, Differentiation - genetics</topic><topic>Antigens, Differentiation - metabolism</topic><topic>B-Lymphocytes - immunology</topic><topic>B-Lymphocytes - metabolism</topic><topic>CpG Islands - genetics</topic><topic>CpG Islands - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>DNA - genetics</topic><topic>DNA - metabolism</topic><topic>Drosophila Proteins</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Interleukin-6 - metabolism</topic><topic>Macrophages, Peritoneal - metabolism</topic><topic>Membrane Glycoproteins - genetics</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>MyD88 protein</topic><topic>Myeloid Differentiation Factor 88</topic><topic>pathogen-associated molecular patterns</topic><topic>Receptors, Cell Surface - genetics</topic><topic>Receptors, Cell Surface - metabolism</topic><topic>Receptors, Immunologic</topic><topic>Signal Transduction</topic><topic>TLR2 protein</topic><topic>TLR4 protein</topic><topic>Toll-Like Receptor 2</topic><topic>Toll-Like Receptor 4</topic><topic>Toll-Like Receptors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schnare, Markus</creatorcontrib><creatorcontrib>Holt†, Agnieszka Czopik</creatorcontrib><creatorcontrib>Takeda, Kiyoshi</creatorcontrib><creatorcontrib>Akira, Shizuo</creatorcontrib><creatorcontrib>Medzhitov, Ruslan</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Current biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schnare, Markus</au><au>Holt†, Agnieszka Czopik</au><au>Takeda, Kiyoshi</au><au>Akira, Shizuo</au><au>Medzhitov, Ruslan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88</atitle><jtitle>Current biology</jtitle><addtitle>Curr Biol</addtitle><date>2000-09-21</date><risdate>2000</risdate><volume>10</volume><issue>18</issue><spage>1139</spage><epage>1142</epage><pages>1139-1142</pages><issn>0960-9822</issn><eissn>1879-0445</eissn><abstract>The innate immune system evolved to recognize conserved microbial products, termed pathogen-associated molecular patterns (PAMPs), which are invariant among diverse groups of microorganisms. PAMPs are recognized by a set of germ-line encoded pattern recognition receptors (PRRs). Among the best characterized PAMPs are bacterial lipopolysaccharide (LPS), peptidoglycan (PGN), mannans, and other constituents of bacterial and fungal cell walls, as well as bacterial DNA. Recognition of bacterial DNA is the most enigmatic of these, as it depends on a particular sequence motif, called the CpG motif, in which an unmethylated CpG present in a particular sequence context accounts for a potent immunostimulatory activity of CpG DNA. Receptor(s) of the innate immune system that mediate recognition of CpG DNA are currently unknown. Here, we report that recognition of CpG DNA requires MyD88, an adaptor protein involved in signal transduction by the Toll-like receptors (TLRs), essential components of innate immune recognition in both Drosophila and mammals [1,2]. 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| source | MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adaptor Proteins, Signal Transducing Animals Antigens, Differentiation - genetics Antigens, Differentiation - metabolism B-Lymphocytes - immunology B-Lymphocytes - metabolism CpG Islands - genetics CpG Islands - immunology Dendritic Cells - metabolism DNA - genetics DNA - metabolism Drosophila Proteins Enzyme-Linked Immunosorbent Assay Interleukin-6 - metabolism Macrophages, Peritoneal - metabolism Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Mice Mice, Knockout MyD88 protein Myeloid Differentiation Factor 88 pathogen-associated molecular patterns Receptors, Cell Surface - genetics Receptors, Cell Surface - metabolism Receptors, Immunologic Signal Transduction TLR2 protein TLR4 protein Toll-Like Receptor 2 Toll-Like Receptor 4 Toll-Like Receptors |
| title | Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88 |
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