| First Author | Buwitt-Beckmann U | Year | 2006 |
| Journal | J Biol Chem | Volume | 281 |
| Issue | 14 | Pages | 9049-57 |
| PubMed ID | 16455646 | Mgi Jnum | J:111575 |
| Mgi Id | MGI:3654418 | Doi | 10.1074/jbc.M512525200 |
| Citation | Buwitt-Beckmann U, et al. (2006) TLR1- and TLR6-independent recognition of bacterial lipopeptides. J Biol Chem 281(14):9049-57 |
| abstractText | Bacterial cell walls contain lipoproteins/peptides, which are strong modulators of the innate immune system. Triacylated lipopeptides are assumed to be recognized by TLR2/TLR1-, whereas diacylated lipopeptides use TLR2/TLR6 heteromers for signaling. Following our initial discovery of TLR6-independent diacylated lipopeptides, we could now characterize di- and triacylated lipopeptides (e.g. Pam(2)C-SK(4), Pam(3)C-GNNDESNISFKEK), which have stimulatory activity in TLR1- and in TLR6-deficient mice. Furthermore, for the first time, we present triacylated lipopeptides with short length ester-bound fatty acids (like PamOct(2)C-SSNASK(4)), which induce no response in TLR1-deficient cells. No differences in the phosphorylation of MAP kinases by lipopeptide analogs having different TLR2-coreceptor usage were observed. Blocking experiments indicated that different TLR2 heteromers recognize their specific lipopeptide ligands independently from each other. In summary, a triacylation pattern is necessary but not sufficient to render a lipopeptide TLR1-dependent, and a diacylation pattern is necessary but not sufficient to render a lipopeptide TLR6-dependent. Contrary to the current model, distinct lipopeptides are recognized by TLR2 in a TLR1- and TLR6-independent manner. |
