Repetitive Elements in Mammalian Telomeres Suppress Bacterial DNA-Induced Immune Activation
Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive ele...
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| Veröffentlicht in: | The Journal of immunology (1950) 2003-08, Vol.171 (3), p.1393-1400 |
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| container_title | The Journal of immunology (1950) |
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| creator | Gursel, Ihsan Gursel, Mayda Yamada, Hiroshi Ishii, Ken J Takeshita, Fumihiko Klinman, Dennis M |
| description | Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-tetrads. Colocalization of CpG DNA with Toll-like receptor 9 in endosomal vesicles is disrupted by these repetitive elements, although cellular binding and uptake remain unchanged. These findings are the first to establish that specific host-derived molecules can down-regulate the innate immune response elicited by a TLR ligand. |
| doi_str_mv | 10.4049/jimmunol.171.3.1393 |
| format | Article |
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Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-tetrads. Colocalization of CpG DNA with Toll-like receptor 9 in endosomal vesicles is disrupted by these repetitive elements, although cellular binding and uptake remain unchanged. These findings are the first to establish that specific host-derived molecules can down-regulate the innate immune response elicited by a TLR ligand.</description><identifier>ISSN: 0022-1767</identifier><identifier>EISSN: 1550-6606</identifier><identifier>DOI: 10.4049/jimmunol.171.3.1393</identifier><identifier>PMID: 12874230</identifier><language>eng</language><publisher>United States: Am Assoc Immnol</publisher><subject><![CDATA[Adjuvants, Immunologic - administration & dosage ; Adjuvants, Immunologic - pharmacology ; Animals ; Cell Line ; CpG Islands - immunology ; DNA, Bacterial - antagonists & inhibitors ; DNA, Bacterial - genetics ; DNA, Bacterial - metabolism ; DNA, Bacterial - pharmacology ; Down-Regulation - immunology ; Endosomes - immunology ; Endosomes - metabolism ; Humans ; Immunity, Innate - genetics ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - pharmacology ; Injections, Intraperitoneal ; Interleukin-12 - antagonists & inhibitors ; Interleukin-12 - biosynthesis ; Lymphocyte Activation - genetics ; Lymphocyte Activation - immunology ; Male ; Membrane Glycoproteins - antagonists & inhibitors ; Membrane Glycoproteins - metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Oligodeoxyribonucleotides - administration & dosage ; Oligodeoxyribonucleotides - pharmacology ; Receptors, Cell Surface - antagonists & inhibitors ; Receptors, Cell Surface - metabolism ; Repetitive Sequences, Nucleic Acid - immunology ; Spleen - cytology ; Spleen - immunology ; Spleen - metabolism ; Telomere - genetics ; Telomere - immunology ; Toll-Like Receptor 9 ; Toll-Like Receptors]]></subject><ispartof>The Journal of immunology (1950), 2003-08, Vol.171 (3), p.1393-1400</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c475t-3aeac0db2a80c1235918a335871ca5b9a3560d431cf692a5d21cd4c414de9b803</citedby><cites>FETCH-LOGICAL-c475t-3aeac0db2a80c1235918a335871ca5b9a3560d431cf692a5d21cd4c414de9b803</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12874230$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gursel, Ihsan</creatorcontrib><creatorcontrib>Gursel, Mayda</creatorcontrib><creatorcontrib>Yamada, Hiroshi</creatorcontrib><creatorcontrib>Ishii, Ken J</creatorcontrib><creatorcontrib>Takeshita, Fumihiko</creatorcontrib><creatorcontrib>Klinman, Dennis M</creatorcontrib><title>Repetitive Elements in Mammalian Telomeres Suppress Bacterial DNA-Induced Immune Activation</title><title>The Journal of immunology (1950)</title><addtitle>J Immunol</addtitle><description>Bacterial DNA contains immunostimulatory CpG motifs that trigger an innate immune response capable of promoting host survival following infectious challenge. Yet CpG-driven immune activation may also have deleterious consequences, ranging from autoimmune disease to death. We find that repetitive elements present at high frequency in mammalian telomeres, but rare in bacteria, down-regulate CpG-induced immune activation. Suppressive activity correlates with the ability of telomeric TTAGGG repeats to form G-tetrads. Colocalization of CpG DNA with Toll-like receptor 9 in endosomal vesicles is disrupted by these repetitive elements, although cellular binding and uptake remain unchanged. These findings are the first to establish that specific host-derived molecules can down-regulate the innate immune response elicited by a TLR ligand.</description><subject>Adjuvants, Immunologic - administration & dosage</subject><subject>Adjuvants, Immunologic - pharmacology</subject><subject>Animals</subject><subject>Cell Line</subject><subject>CpG Islands - immunology</subject><subject>DNA, Bacterial - antagonists & inhibitors</subject><subject>DNA, Bacterial - genetics</subject><subject>DNA, Bacterial - metabolism</subject><subject>DNA, Bacterial - pharmacology</subject><subject>Down-Regulation - immunology</subject><subject>Endosomes - immunology</subject><subject>Endosomes - metabolism</subject><subject>Humans</subject><subject>Immunity, Innate - genetics</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - pharmacology</subject><subject>Injections, Intraperitoneal</subject><subject>Interleukin-12 - antagonists & inhibitors</subject><subject>Interleukin-12 - biosynthesis</subject><subject>Lymphocyte Activation - genetics</subject><subject>Lymphocyte Activation - immunology</subject><subject>Male</subject><subject>Membrane Glycoproteins - antagonists & inhibitors</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Knockout</subject><subject>Oligodeoxyribonucleotides - administration & dosage</subject><subject>Oligodeoxyribonucleotides - pharmacology</subject><subject>Receptors, Cell Surface - antagonists & inhibitors</subject><subject>Receptors, Cell Surface - metabolism</subject><subject>Repetitive Sequences, Nucleic Acid - immunology</subject><subject>Spleen - cytology</subject><subject>Spleen - immunology</subject><subject>Spleen - metabolism</subject><subject>Telomere - genetics</subject><subject>Telomere - immunology</subject><subject>Toll-Like Receptor 9</subject><subject>Toll-Like Receptors</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtvEzEURi1ERdPCL0BCXsFqwr1-zGMZSguR2iJBWbGwHM8NdWXPTMczRPz7OkoQ7Fh9m3OPrg5jrxGWClTz_sHHOHd9WGKFS7lE2chnbIFaQ1GWUD5nCwAhCqzK6pSdpfQAACUI9YKdoqgrJSQs2I-vNNDkJ_-L-GWgSN2UuO_4jY3RBm87fkehjzRS4t_mYcib-AfrJhq9Dfzj7apYd-3sqOXr_TvEVy7L7OT77iU72dqQ6NVxz9n3q8u7i8_F9ZdP64vVdeFUpadCWrIO2o2wNTgUUjdYWyl1XaGzetNYqUtolUS3LRthdSvQtcopVC01mxrkOXt78A5j_zhTmkz0yVEItqN-TqaSqkEF8r8g1tkGoDMoD6Ab-5RG2pph9NGOvw2C2cc3f-KbHN9Is4-fr94c9fMmUvv35lg7A-8OwL3_eb_zI5mUI4eMo9ntdv-ongBz-JAE</recordid><startdate>20030801</startdate><enddate>20030801</enddate><creator>Gursel, Ihsan</creator><creator>Gursel, Mayda</creator><creator>Yamada, Hiroshi</creator><creator>Ishii, Ken J</creator><creator>Takeshita, Fumihiko</creator><creator>Klinman, Dennis M</creator><general>Am Assoc Immnol</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>7QL</scope><scope>7T5</scope><scope>C1K</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20030801</creationdate><title>Repetitive Elements in Mammalian Telomeres Suppress Bacterial DNA-Induced Immune Activation</title><author>Gursel, Ihsan ; 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| subjects | Adjuvants, Immunologic - administration & dosage Adjuvants, Immunologic - pharmacology Animals Cell Line CpG Islands - immunology DNA, Bacterial - antagonists & inhibitors DNA, Bacterial - genetics DNA, Bacterial - metabolism DNA, Bacterial - pharmacology Down-Regulation - immunology Endosomes - immunology Endosomes - metabolism Humans Immunity, Innate - genetics Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - pharmacology Injections, Intraperitoneal Interleukin-12 - antagonists & inhibitors Interleukin-12 - biosynthesis Lymphocyte Activation - genetics Lymphocyte Activation - immunology Male Membrane Glycoproteins - antagonists & inhibitors Membrane Glycoproteins - metabolism Mice Mice, Inbred BALB C Mice, Knockout Oligodeoxyribonucleotides - administration & dosage Oligodeoxyribonucleotides - pharmacology Receptors, Cell Surface - antagonists & inhibitors Receptors, Cell Surface - metabolism Repetitive Sequences, Nucleic Acid - immunology Spleen - cytology Spleen - immunology Spleen - metabolism Telomere - genetics Telomere - immunology Toll-Like Receptor 9 Toll-Like Receptors |
| title | Repetitive Elements in Mammalian Telomeres Suppress Bacterial DNA-Induced Immune Activation |
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