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rdf:type |
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lifeskim:mentions |
umls-concept:C0010823,
umls-concept:C0205224,
umls-concept:C0439662,
umls-concept:C0449432,
umls-concept:C0877837,
umls-concept:C0963057,
umls-concept:C1179435,
umls-concept:C1524073,
umls-concept:C1548799,
umls-concept:C1705248,
umls-concept:C1880266
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pubmed:issue |
10
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pubmed:dateCreated |
2004-3-10
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pubmed:databankReference |
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pubmed:abstractText |
Several subsets of dendritic cells have been shown to produce type I IFN in response to viral infections, thereby assisting the natural killer cell-dependent response that eliminates the pathogen. Type I IFN production can be induced both by unmethylated CpG-oligodeoxynucleotide and by double-stranded RNA. Here, we describe a codominant CpG-ODN unresponsive phenotype that results from an N-ethyl-N-nitrosourea-induced missense mutation in the Tlr9 gene (Tlr9(CpG1)). Mice homozygous for the Tlr9(CpG1) allele are highly susceptible to mouse cytomegalovirus infection and show impaired infection-induced secretion of IFN-alpha/beta and natural killer cell activation. We also demonstrate that both the Toll-like receptor (TLR) 9 --> MyD88 and TLR3 --> Trif signaling pathways are activated in vivo on viral inoculation, and that each pathway contributes to innate defense against systemic viral infection. Whereas both pathways lead to type I IFN production, neither pathway offers full protection against mouse cytomegalovirus infection in the absence of the other. The Tlr9(CpG1) mutation alters a leucine-rich repeat motif and lies within a receptor domain that is conserved within the evolutionary cluster encompassing TLRs 7, 8, and 9. In other TLRs, including three mouse-specific TLRs described in this paper, the affected region is not represented. The phenotypic effect of the Tlr9(CpG1) allele thus points to a critical role for TLR9 in viral sensing and identifies a vulnerable amino acid within the ectodomain of three TLR proteins, essential for a ligand response.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-10996797,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-11022119,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-11130078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-11326273,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-11340207,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-11435470,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-11607032,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-11713464,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-11854364,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-11950999,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12060703,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12088676,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12115616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12488506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12495732,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12496964,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12524386,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12682109,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12819664,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12855817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12872135,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12900271,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12900525,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-12935356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-14512563,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-14563635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-7520526,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-7561678,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-7583641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-8638399,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-8648121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-9104805,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-9697844,
http://linkedlifedata.com/resource/pubmed/commentcorrection/14993594-9822609
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation,
http://linkedlifedata.com/resource/pubmed/chemical/CPG-oligonucleotide,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myd88 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88,
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Tlr9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 3,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptor 9,
http://linkedlifedata.com/resource/pubmed/chemical/Toll-Like Receptors
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0027-8424
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pubmed:author |
pubmed-author:AlexopoulouLenaL,
pubmed-author:BeutlerBruceB,
pubmed-author:CrozatKarineK,
pubmed-author:FlavellRichard ARA,
pubmed-author:GeorgelPhilippeP,
pubmed-author:GoodeJasonJ,
pubmed-author:HoebeKasperK,
pubmed-author:JanssenEdithE,
pubmed-author:LüZ BZB,
pubmed-author:MuddSuzanneS,
pubmed-author:ShamelLouisL,
pubmed-author:SovathSosathyaS,
pubmed-author:TabetaKoichiK
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pubmed:issnType |
Print
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pubmed:day |
9
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pubmed:volume |
101
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3516-21
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:14993594-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:14993594-Amino Acid Sequence,
pubmed-meshheading:14993594-Animals,
pubmed-meshheading:14993594-Antigens, Differentiation,
pubmed-meshheading:14993594-Cytokines,
pubmed-meshheading:14993594-Cytomegalovirus Infections,
pubmed-meshheading:14993594-DNA, Complementary,
pubmed-meshheading:14993594-DNA-Binding Proteins,
pubmed-meshheading:14993594-Immunity, Innate,
pubmed-meshheading:14993594-Killer Cells, Natural,
pubmed-meshheading:14993594-Membrane Glycoproteins,
pubmed-meshheading:14993594-Mice,
pubmed-meshheading:14993594-Mice, Inbred BALB C,
pubmed-meshheading:14993594-Mice, Inbred C57BL,
pubmed-meshheading:14993594-Mice, Knockout,
pubmed-meshheading:14993594-Mice, Mutant Strains,
pubmed-meshheading:14993594-Molecular Sequence Data,
pubmed-meshheading:14993594-Mutation, Missense,
pubmed-meshheading:14993594-Myeloid Differentiation Factor 88,
pubmed-meshheading:14993594-Oligodeoxyribonucleotides,
pubmed-meshheading:14993594-Phenotype,
pubmed-meshheading:14993594-Point Mutation,
pubmed-meshheading:14993594-Receptors, Cell Surface,
pubmed-meshheading:14993594-Receptors, Immunologic,
pubmed-meshheading:14993594-Sequence Homology, Amino Acid,
pubmed-meshheading:14993594-Signal Transduction,
pubmed-meshheading:14993594-Toll-Like Receptor 3,
pubmed-meshheading:14993594-Toll-Like Receptor 9,
pubmed-meshheading:14993594-Toll-Like Receptors
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pubmed:year |
2004
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pubmed:articleTitle |
Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection.
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pubmed:affiliation |
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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