Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4

被引：1238

作者：

Kayagaki, Nobuhiko ^{[1
]}

Wong, Michael T. ^{[1
]}

Stowe, Irma B. ^{[1
]}

Ramani, Sree Ranjani ^{[2
]}

Gonzalez, Lino C. ^{[2
]}

Akashi-Takamura, Sachiko ^{[3
]}

Miyake, Kensuke ^{[3
]}

Zhang, Juan ^{[4
]}

Lee, Wyne P. ^{[4
]}

Muszynski, Artur ^{[5
]}

Forsberg, Lennart S. ^{[5
]}

Carlson, Russell W. ^{[5
]}

Dixit, Vishva M. ^{[1
]}

机构：

[1] Genentech Inc, Dept Physiol Chem, San Francisco, CA 94080 USA

[2] Genentech Inc, Dept Prot Chem, San Francisco, CA 94080 USA

[3] Univ Tokyo, Dept Microbiol & Immunol, Ctr Expt Med & Syst Biol, Div Innate Immun,Lab Innate Immun,Inst Med Sci, Tokyo 1088639, Japan

[4] Genentech Inc, Dept Immunol, San Francisco, CA 94080 USA

[5] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA

来源：

SCIENCE | 2013年 / 341卷 / 6151期

基金：

日本学术振兴会;

关键词：

BACTERIAL LIPOPOLYSACCHARIDE; PATTERN-RECOGNITION; IMMUNE RECOGNITION; INTERLEUKIN-1-BETA; CASPASE-11; FLAGELLIN; PROTEASE; TOLL; RECEPTORS; IPAF;

D O I：

10.1126/science.1240248

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1246 / 1249

页数：4

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