Linked Life Data

19573927

Source:http://linkedlifedata.com/resource/pubmed/id/19573927

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2009-8-24
pubmed:abstractText
Similar to mammalian species, chickens show marked immunological responses to CpG oligodeoxynucleotides (ODNs) both in vivo and in vitro. In mammals, the receptor for ODNs has been demonstrated to be TLR9; however, an orthologue to mammalian TLR9 is absent in the chicken genome. In this study, chicken TLRs 7, 15 and 21 were expressed in mammalian HEK-293T cells; expression of TLR21 but not TLR7 or 15 resulted in marked NF-kappaB activation upon stimulation with exogenous ODN. This activation was not observed when cells were stimulated by TLR agonists other than ODNs. In addition, responsiveness of the ectopically expressed TLR21 demonstrated similar kinetics of activation as reported for mammalian TLR9 and was dependent on the nucleotide sequence of the ODN. The same ODN specificity was observed for chicken HD11 macrophage when ODN mediated activation was monitored by up-regulation of IL1, IL6 and iNOS transcripts. Furthermore, when TLR21, but not TLR15, was partially silenced in HD11 cells by RNA interference, ODN mediated responses were reduced. TLR21-mediated NF-kappaB activation in HEK-293T cells was inhibited by bafilomycin A suggesting that endosomal maturation is required for TLR21 activation and observations by confocal microscopy and digestion with endoglycosidase H suggest TLR21 localizes to the endoplasmic reticulum (ER) of resting cells. Expression of TLR21 transcripts was found in all chicken tissues examined but was significantly less in the lung and small intestine of newly hatched birds. Two of the leucine rich repeat regions (LRRs) of TLR21 showed homology with a LRR conserved within mammalian TLR9 and implicated in ligand binding. We hypothesize that avian TLR21 plays a similar role to that of mammalian TLR9 and enables recognition of microbial DNA as a danger signal resulting in downstream innate and adaptive immune responses.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1872-9142
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3163-70
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Chicken TLR21 acts as a functional homologue to mammalian TLR9 in the recognition of CpG oligodeoxynucleotides.
pubmed:affiliation
Vaccine and Infectious Diseases Organization, University of Saskatchewan, 120 Veterinary Road, Saskatoon, Saskatchewan, Canada S7N 5E3. robert.brownlie@usask.ca
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't