Noncanonical inflammasome activation by intracellular LPS independent of TLR4.
Science
; 341(6151): 1246-9, 2013 Sep 13.
Article
en En
| MEDLINE
| ID: mdl-23887873
ABSTRACT
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 polyinosinicpolycytidylic acid [poly(IC)] 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptor Toll-Like 4
/
Inflamasomas
/
Inmunidad Innata
/
Lípido A
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Macrófagos
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos