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Publication : Cutting edge: activation of murine TLR8 by a combination of imidazoquinoline immune response modifiers and polyT oligodeoxynucleotides.

First Author  Gorden KK Year  2006
Journal  J Immunol Volume  177
Issue  10 Pages  6584-7
PubMed ID  17082568 Mgi Jnum  J:140503
Mgi Id  MGI:3814004 Doi  10.4049/jimmunol.177.10.6584
Citation  Gorden KK, et al. (2006) Cutting edge: activation of murine TLR8 by a combination of imidazoquinoline immune response modifiers and polyT oligodeoxynucleotides. J Immunol 177(10):6584-7
abstractText  Synthetic immune response modifiers (IRM) such as imidazoquinolines can selectively activate human TLR7 or TLR8. Although these endosomal TLRs are close relatives, TLR7-deficient mice are unresponsive to TLR8 agonist IRMs. Similarly, natural ssRNA cannot activate murine TLR8, leading to the belief that murine TLR8 is nonfunctional. In this study, we transfected HEK293 cells with murine TLR8 and NF-kappaB reporter constructs and stimulated them with combinations of IRM and oligodeoxynucleotides (ODNs). When stimulated with TLR7 or TLR8 agonists alone, no NF-kappaB response was observed. However, a combination of polyT ODN plus the TLR8 agonist activated NF-kappaB, whereas polyT ODN plus the TLR7 agonist did not activate. Primary mouse cells responded to the IRM/polyT ODN by secreting TNF. Cells from TLR7(-/-) and TLR9(-/-) mice responded to the IRM/polyT ODN combination, whereas MyD88(-/-) cells did not respond. In conclusion, this study demonstrates for the first time that mouse TLR8 is functional.
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