Journal ArticleDOI
Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway.
Laurence Arbibe,Jean Paul Mira,Jean Paul Mira,Nicole Teusch,Lois Kline,Mausumee Guha,Nigel Mackman,Paul J. Godowski,Richard J. Ulevitch,Ulla G. Knaus +9 more
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TLDR
TLR2 stimulation by Staphylococcus aureus induces a fast and transient activation of the Rho GTPases Rac1 and Cdc42 in the human monocytic cell line THP-1 and in 293 cells expressing TLR2, and Rac1 controls a second, IκB–independent, pathway to NF-κB activation and is essential in innate immune cell signaling via TLR 2.Abstract:
Mammalian Toll-like receptors (TLRs) are expressed on innate immune cells and respond to the membrane components of Gram-positive or Gram-negative bacteria. When activated, they convey signals to transcription factors that orchestrate the inflammatory response. However, the intracellular signaling events following TLR activation are largely unknown. Here we show that TLR2 stimulation by Staphylococcus aureus induces a fast and transient activation of the Rho GTPases Rac1 and Cdc42 in the human monocytic cell line THP-1 and in 293 cells expressing TLR2. Dominant-negative Rac1N17, but not dominant-negative Cdc42N17, block nuclear factor-κB (NF-κB) transactivation. S. aureus stimulation causes the recruitment of active Rac1 and phosphatidylinositol-3 kinase (PI3K) to the TLR2 cytosolic domain. Tyrosine phosphorylation of TLR2 is required for assembly of a multiprotein complex that is necessary for subsequent NF-κB transcriptional activity. A signaling cascade composed of Rac1, PI3K and Akt targets nuclear p65 transactivation independently of IκBα degradation. Thus Rac1 controls a second, IκB–independent, pathway to NF-κB activation and is essential in innate immune cell signaling via TLR2.read more
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Journal ArticleDOI
β-PIX and Rac1 GTPase Mediate Trafficking and Negative Regulation of NOD2
Julia Eitel,Matthias Krüll,Andreas C. Hocke,Philippe Dje N'Guessan,Janine Zahlten,Bernd Schmeck,Hortense Slevogt,Stefan Hippenstiel,Norbert Suttorp,Bastian Opitz +9 more
TL;DR: The data indicate that β-PIX and Rac1 mediate trafficking and negative regulation of NOD2-dependent signaling which is different from Rac1’s positive regulatory role in TLR2 signaling.
Journal ArticleDOI
Apoptosis in infectious disease: how bacteria interfere with the apoptotic apparatus.
TL;DR: The field of bacterial inhibition of apoptosis is structure and recent advancements in knowledge of how chlamydiae interfere with the host cell’s capacity to undergo apoptosis are discussed.
Journal ArticleDOI
Toll-like receptor 2 deficiency delays pneumococcal phagocytosis and impairs oxidative killing by granulocytes.
Maryse Letiembre,Hakim Echchannaoui,Philipp Bachmann,Fabrizia Ferracin,Concepción Nieto,Manuel Espinosa,Regine Landmann +6 more
TL;DR: Phagocytosis and killing of Streptococcus pneumoniae was compared in blood-derived wild-type and Toll-like receptor 2-deficient polymorphonuclear leukocytes (PMN), suggesting that TLR2 modulates bacterial clearance in PMN.
Journal ArticleDOI
The molecular basis of induction and formation of tunneling nanotubes
TL;DR: HIV Nef and M-Sec can induce the formation of TNTs in coordination with the remodeling of the actin cytoskeleton and vesicle trafficking, and these studies have revealed key molecules for their induction and/or formation.
Journal ArticleDOI
Cooperative Interactions between Flagellin and SopE2 in the Epithelial Interleukin-8 Response to Salmonella enterica Serovar Typhimurium Infection
Fu-Chen Huang,Fu-Chen Huang,Adam Werne,Qian Li,Edouard E. Galyov,W. Allan Walker,Bobby J. Cherayil +6 more
TL;DR: Results indicate that flagellin and SopE2 interact functionally at multiple levels to increase IL-8 secretion by epithelial cells—flagell in facilitating the translocation of SopE 2, and Sop E2 enhancing signaling pathways activated by flageLLin.
References
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A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
TL;DR: The cloning and characterization of a human homologue of the Drosophila toll protein (Toll) is reported, which has been shown to induce the innate immune response in adult Dosophila.
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Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components.
Osamu Takeuchi,Katsuaki Hoshino,Taro Kawai,Hideki Sanjo,Haruhiko Takada,Tomohiko Ogawa,Kiyoshi Takeda,Shizuo Akira +7 more
TL;DR: It is demonstrated that TLR2 and TLR4 recognize different bacterial cell wall components in vivo andTLR2 plays a major role in Gram-positive bacterial recognition.
Journal ArticleDOI
Toll-like receptors in the induction of the innate immune response
Alan Aderem,Richard J. Ulevitch +1 more
TL;DR: A group of proteins that comprise the Toll or Toll-like family of receptors perform this role in vertebrate and invertebrate organisms and it is therefore not surprising that studies of the mechanism by which they act has revealed new and important insights into host defence.
Journal ArticleDOI
Rho GTPases and signaling networks
TL;DR: The Rho GTPases form a subgroup of the Ras superfamily of 20- to 30-kD GTP-binding proteins that have been shown to regulate a wide spectrum of cellular functions, and some of the more recent exciting findings hinting at novel, unanticipated functions of the RhoGTPases are summarized.
Journal ArticleDOI
NF-κB activation by tumour necrosis factor requires the Akt serine–threonine kinase
Osman N. Ozes,Lindsey D. Mayo,Jason A. Gustin,Susan R. Pfeffer,Lawrence M. Pfeffer,David B. Donner +5 more
TL;DR: It is shown that the Akt serine–threonine kinase is involved in the activation of NF-κB by tumour necrosis factor (TNF), and that Akt is part of a signalling pathway that is necessary for inducing key immune and inflammatory responses.