| First Author | Piao W | Year | 2015 |
| Journal | Cell Rep | Volume | 11 |
| Issue | 12 | Pages | 1941-52 |
| PubMed ID | 26095366 | Mgi Jnum | J:224868 |
| Mgi Id | MGI:5689223 | Doi | 10.1016/j.celrep.2015.05.035 |
| Citation | Piao W, et al. (2015) A Decoy Peptide that Disrupts TIRAP Recruitment to TLRs Is Protective in a Murine Model of Influenza. Cell Rep 11(12):1941-52 |
| abstractText | Toll-like receptors (TLRs) activate distinct, yet overlapping sets of signaling molecules, leading to inflammatory responses to pathogens. Toll/interleukin-1 receptor (TIR) domains, present in all TLRs and TLR adapters, mediate protein interactions downstream of activated TLRs. A peptide library derived from TLR2 TIR was screened for inhibition of TLR2 signaling. Cell-permeable peptides derived from the D helix and the segment immediately N-terminal to the TLR2 TIR domain potently inhibited TLR2-mediated cytokine production. The D-helix peptide, 2R9, also potently inhibited TLR4, TLR7, and TLR9, but not TLR3 or TNF-alpha signaling. Cell imaging, co-immunoprecipitation, and in vitro studies demonstrated that 2R9 preferentially targets TIRAP. 2R9 diminished systemic cytokine responses elicited in vivo by synthetic TLR2 and TLR7 agonists; it inhibited the activation of macrophages infected with influenza strain A/PR/8/34 (PR8) and significantly improved the survival of PR8-infected mice. Thus, 2R9 represents a TLR-targeting agent that blocks protein interactions downstream of activated TLRs. |
