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Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4

by Miyake, Kensuke , Forsberg, Lennart S. , Stowe, Irma B. , Dixit, Vishva M. , Lee, Wyne P. , Zhang, Juan , Gonzalez, Lino C. , Carlson, Russell W. , Kayagaki, Nobuhiko , Muszyński, Artur , Akashi-Takamura, Sachiko , Wong, Michael T. , Ramani, Sree Ranjani

in Activation / Agonists / Animals / Bacteria / Biochemistry / caspase-11 / Caspases - biosynthesis / Cellular biology / Cholera Toxin - immunology / Cytoplasm / Disease Models, Animal / E coli / Escherichia coli - immunology / Escherichia coli Infections - genetics / Escherichia coli Infections - immunology / Gram negative bacteria / immune response / Immune system / Immune systems / Immunity, Innate / Inflammasomes - immunology / innate immunity / Lethality / Lipid A - genetics / Lipid A - immunology / Lipids / lipopolysaccharides / Macrophages / Macrophages - immunology / Mice / Mice, Mutant Strains / Mutation / Neurons / Online / Proteins / Rodents / Salmonella Infections - immunology / Salmonella typhimurium - immunology / Secretion / Sepsis / Sepsis - immunology / Signals / Toll-like receptor 4 / Toll-Like Receptor 4 - immunology / Transfection

2013

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Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4

2013

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Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4

2013

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Journal Article

Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4

Miyake, Kensuke,

Forsberg, Lennart S.,

Stowe, Irma B.,

Dixit, Vishva M.,

Lee, Wyne P.,

Zhang, Juan,

Gonzalez, Lino C.,

Carlson, Russell W.,

Kayagaki, Nobuhiko,

Muszyński, Artur,

Akashi-Takamura, Sachiko,

Wong, Michael T.,

Ramani, Sree Ranjani

2013

Overview

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.

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Publisher

American Association for the Advancement of Science,The American Association for the Advancement of Science

Subject

/ Animals

/ Caspases - biosynthesis