Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-3-6
pubmed:abstractText
The TLRs 7, 8, and 9 stimulate innate immune responses upon recognizing pathogen nucleic acids. U-rich RNA sequences were recently discovered that stimulate human TLR7/8-mediated or murine TLR7-mediated immune effects. In this study we identified single-stranded RNA sequences containing defined sequence motifs that either preferentially activate human TLR8-mediated as opposed to TLR7- or TLR7/8-mediated immune responses. The identified TLR8 RNA motifs signal via TLR8 and fail to induce IFN-alpha from TLR7-expressing plasmacytoid dendritic cells but induce the secretion of Th1-like and proinflammatory cytokines from TLR8-expressing immune cells such as monocytes or myeloid dendritic cells. In contrast, RNA sequences containing the TLR7/8 motif signal via TLR7 and TLR8 and stimulate cytokine secretion from both TLR7- and TLR8-positive immunocytes. The TLR8-specific RNA sequences are able to trigger cytokine responses from human and bovine but not from mouse, rat, and porcine immune cells, suggesting that these species lack the capability to respond properly to TLR8 RNA ligands. In summary, we describe two classes of single-stranded TLR7/8 and TLR8 RNA agonists with diverse target cell and species specificities and immune response profiles.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
180
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3729-38
pubmed:meshHeading
pubmed-meshheading:18322178-Animals, pubmed-meshheading:18322178-Base Sequence, pubmed-meshheading:18322178-Cattle, pubmed-meshheading:18322178-Cell Line, pubmed-meshheading:18322178-Dinucleoside Phosphates, pubmed-meshheading:18322178-Female, pubmed-meshheading:18322178-Humans, pubmed-meshheading:18322178-Interferon-alpha, pubmed-meshheading:18322178-Leukocytes, Mononuclear, pubmed-meshheading:18322178-Ligands, pubmed-meshheading:18322178-Male, pubmed-meshheading:18322178-Mice, pubmed-meshheading:18322178-Mice, Inbred C57BL, pubmed-meshheading:18322178-Mice, Knockout, pubmed-meshheading:18322178-Oligoribonucleotides, pubmed-meshheading:18322178-Rats, pubmed-meshheading:18322178-Rats, Sprague-Dawley, pubmed-meshheading:18322178-Sequence Analysis, RNA, pubmed-meshheading:18322178-Swine, pubmed-meshheading:18322178-Toll-Like Receptor 8, pubmed-meshheading:18322178-Tumor Necrosis Factor-alpha
pubmed:year
2008
pubmed:articleTitle
Identification of RNA sequence motifs stimulating sequence-specific TLR8-dependent immune responses.
pubmed:affiliation
Coley Pharmaceutical GmbH, Düsseldorf, Germany.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural