Linked Life Data

15934170

Source:http://linkedlifedata.com/resource/pubmed/id/15934170

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2005-6-3
pubmed:abstractText
The innate immune system senses pathogens largely through signals initiated by a collection of phylogenetically related proteins known as "Toll-like receptors" (TLRs), of which ten representatives are encoded in the human genome. The sensing role of the TLRs first came to light when one member of this family, TLR4, was shown to serve the detection of endotoxin (lipopolysaccharide; LPS) in mice. This discovery was based upon positional cloning of a spontaneous mutation affecting a locus known as Lps. The recognition specificities of other TLRs have since been established by reverse genetic methods. The understanding of the biochemical circuitry that maintains the innate capacity for immune recognition and response has loomed as the next hurdle in the field. A total of five adapter proteins with cytoplasmic domain homology to the TLRs are known to exist in mammals. These proteins are not entirely promiscuous in their interaction with TLRs, but rather, show preferential association with individual family members, giving a particular character to the signals that distinct micro-organisms initiate. The adaptive immune response is dependent upon upregulation of costimulatory molecules (UCM) such as CD80 and CD86. Very recently, it has been shown that this upregulation is dependent upon an adapter encoded by a locus known as Lps2, known as Trif or Ticam-1, and upon type I interferon receptor signaling. LPS and dsRNA both signal via Trif, but dsRNA has an accessory pathway for UCM, that is independent of both Trif/Ticam-1 and the known dsRNA receptor, TLR3. Other key innate immunity genes have also been disclosed by germline mutagenesis, and are discussed in the present review.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing, http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Vesicular..., http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation, http://linkedlifedata.com/resource/pubmed/chemical/MYD88 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Myeloid Differentiation Factor 88, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Interleukin-1, http://linkedlifedata.com/resource/pubmed/chemical/TICAM1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/TIRAP protein, human, http://linkedlifedata.com/resource/pubmed/chemical/TRAM protein, ER, mammalian
pubmed:status
MEDLINE
pubmed:issn
0065-2598
pubmed:author
pubmed:issnType
Print
pubmed:volume
560
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29-39
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Genetic analysis of innate immunity: identification and function of the TIR adapter proteins.
pubmed:affiliation
Scripps Research Institute, Department of Immunology, IMM-31, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA. bruce@scripps.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review, Research Support, N.I.H., Extramural