| First Author | Kayagaki N | Year | 2013 |
| Journal | Science | Volume | 341 |
| Issue | 6151 | Pages | 1246-9 |
| PubMed ID | 23887873 | Mgi Jnum | J:201075 |
| Mgi Id | MGI:5510905 | Doi | 10.1126/science.1240248 |
| Citation | Kayagaki N, et al. (2013) Noncanonical inflammasome activation by intracellular LPS independent of TLR4. Science 341(6151):1246-9 |
| abstractText | Gram-negative bacteria including Escherichia coli, Citrobacter rodentium, Salmonella typhimurium, and Shigella flexneri are sensed in an ill-defined manner by an intracellular inflammasome complex that activates caspase-11. We show that macrophages loaded with synthetic lipid A, E. coli lipopolysaccharide (LPS), or S. typhimurium LPS activate caspase-11 independently of the LPS receptor Toll-like receptor 4 (TLR4). Consistent with lipid A triggering the noncanonical inflammasome, LPS containing a divergent lipid A structure antagonized caspase-11 activation in response to E. coli LPS or Gram-negative bacteria. Moreover, LPS-mutant E. coli failed to activate caspase-11. Tlr4(-/-) mice primed with TLR3 agonist polyinosinic:polycytidylic acid [poly(I:C)] to induce pro-caspase-11 expression were as susceptible as wild-type mice were to sepsis induced by E. coli LPS. These data unveil a TLR4-independent mechanism for innate immune recognition of LPS. |
