Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4

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

doi:10.1126/science.1240248

Abstract

Move Over, TLR4 The innate immune system senses bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 (TLR4) (see the Perspective by Kagan ). However, Kayagaki et al. (p 1246 , published online 25 July) and Hagar et al. (p. 1250 ) report that the hexa-acyl lipid A component of LPS from Gramnegative bacteria is able to access the cytoplasm and activate caspase-11 to signal immune responses independently of TLR4. Mice that lack caspase-11 are resistant to LPS-induced lethality, even in the presence of TLR4.

Keywords

TLR4InflammasomeLipopolysaccharideInnate immune systemCytoplasmLipid AToll-like receptorIntracellularImmune systemCell biologyChemistryReceptorMicrobiologySignal transductionBiologyImmunologyBiochemistry

Affiliated Institutions

Related Publications

IL-1 Receptor-Associated Kinase Modulates Host Responsiveness to Endotoxin

Jennifer L. Swantek , May F. Tsen , Melanie H. Cobb +1 more

Abstract Endotoxin triggers many of the inflammatory, hemodynamic, and hematological derangements of Gram-negative septic shock. Recent genetic studies in mice have identified t...

2000 The Journal of Immunology 283 citations

Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-γ: a molecular basis for priming and synergism with bacterial lipopolysaccharide

Daniela Bosisio , Nadia Polentarutti , Marina Sironi +6 more

Abstract In human monocytes and macrophages, interferon-γ (IFNγ) augmented mRNA and surface expression of toll-like receptor 4 (TLR4), a crucial component of the signaling recep...

2002 Blood 280 citations

Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments

Parviz Ahmad‐Nejad , Hans Häcker , Mark Rutz +3 more

Recognition by innate immune cells of the pathogen associated molecular patterns (PAMP) lipopolysaccharide (LPS) from Gram-negative bacteria and bacterial CpG-DNA depends on Tol...

2002 European Journal of Immunology 711 citations

Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in <i>Tlr4</i> Gene

Alexander Poltorak , Xiaolong He , Irina Smirnova +11 more

Mutations of the gene Lps selectively impede lipopolysaccharide (LPS) signal transduction in C3H/HeJ and C57BL/10ScCr mice, rendering them resistant to endotoxin yet highly susc...

1998 Science 7517 citations

Differential Roles of TLR2 and TLR4 in Recognition of Gram-Negative and Gram-Positive Bacterial Cell Wall Components

Osamu Takeuchi , Katsuaki Hoshino , Taro Kawai +5 more

Toll-like receptor (TLR) 2 and TLR4 are implicated in the recognition of various bacterial cell wall components, such as lipopolysaccharide (LPS). To investigate in vivo roles o...

1999 Immunity 3334 citations

Publication Info

Year: 2013
Type: article
Volume: 341
Issue: 6151
Pages: 1246-1249
Citations: 1477
Access: Closed

External Links

View on DOI.org

Social Impact

Altmetric

Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

1477

OpenAlex

Cite This

APA Style

                            
                                
                                    Nobuhiko Kayagaki, 
                                
                                    Michael T. Wong, 
                                
                                    Irma B. Stowe
                                
                                et al.
                            
                            (2013). 
                            Noncanonical Inflammasome Activation by Intracellular LPS Independent of TLR4. 
                            Science
                            , 341
                            (6151)
                            , 1246-1249.
                            https://doi.org/10.1126/science.1240248
                        

Identifiers

DOI: 10.1126/science.1240248