TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human macrophages

Gantier, M. P., Tong, S., Behlke, M. A., Xu, D., Phipps, S., Foster, P. S. and Williams, B. R. G. (2008) TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human macrophages. Journal of Immunology, 180 4: 2117-2124.

Author Gantier, M. P.
Tong, S.
Behlke, M. A.
Xu, D.
Phipps, S.
Foster, P. S.
Williams, B. R. G.
Title TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human macrophages
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2008-02
Sub-type Article (original research)
Volume 180
Issue 4
Start page 2117
End page 2124
Total pages 8
Place of publication Bethesda, MD, United States
Publisher American Association of Immunologists
Language eng
Formatted abstract
Human TLR7 and 8 (hTLR7/8) have been implicated in the sequence-dependent detection of RNA oligonucleotides in immune cells. Although hTLR7 sequence-specific sensing of short RNAs has been inferred from studies of murine TLR7, this has yet to be established for hTLR7. We found that different short ssRNA sequences selectively induced either TNF-α or IFN-α in human PBMCs. The sequence-specific TNF-α response to ssRNAs observed in PBMCs could be replicated in activated human macrophage-like (THP-1) cells pretreated with IFN-γ. Surprisingly, suppression of hTLR7 expression by RNA interference in this model reduced sensing of all immunostimulatory ssRNAs tested. Modulation of the relative expression ratio of hTLR7 to hTLR8 in THP-1 cells correlated with differential sensing of immunostimulatory sequences. Furthermore, the sequence-specific IFN-α induction profile in human PBMCs was accurately modeled by a sequence-specific activation of murine TLR7 in mouse macrophages. Thus, we demonstrate for the first time that hTLR7 is involved in sequence-specific sensing of ssRNAs. We establish a novel cell model for the prediction of TNF-α induction by short RNAs in human macrophages. Our results suggest that differential sequence-specific sensing of RNA oligonucleotides between human and mouse macrophages is due to the modulation of TLR7 sensing by human TLR8.
Keyword Toll-like Receptors
Synthetic Sirna
Interfering Rna
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
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Created: Wed, 09 Mar 2011, 14:28:55 EST