Journal ArticleDOI
Essential role of MD-2 in LPS responsiveness and TLR4 distribution.
Yoshinori Nagai,Sachiko Akashi,Masakazu Nagafuku,Masato Ogata,Yoichiro Iwakura,Shizuo Akira,Toshio Kitamura,Atsushi Kosugi,Masao Kimoto,Kensuke Miyake +9 more
TLDR
It is found that in MD-2−/− embryonic fibroblasts, TLR4 was not able to reach the plasma membrane and predominantly resided in the Golgi apparatus, whereas TLR3 was distributed at the leading edge surface of cells in wild-type embryonic fibrablasts andMD-2 is essential for correct intracellular distribution and LPS-recognition ofTLR4.Abstract:
Toll-like receptor 4 (TLR4) mediates lipopolysaccharide (LPS) signaling in a variety of cell types. MD-2 is associated with the extracellular domain of TLR4 and augments TLR4-dependent LPS responses in vitro. We show here that MD-2(-/-) mice do not respond to LPS, do survive endotoxic shock but are susceptible to Salmonella typhimurium infection. We found that in MD-2(-/-) embryonic fibroblasts, TLR4 was not able to reach the plasma membrane and predominantly resided in the Golgi apparatus, whereas TLR4 was distributed at the leading edge surface of cells in wild-type embryonic fibroblasts. Thus, MD-2 is essential for correct intracellular distribution and LPS-recognition of TLR4.read more
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Toll-like receptors.
TL;DR: This unit discusses mammalian Toll receptors (TLR1‐10) that have an essential role in the innate immune recognition of microorganisms and are discussed are TLR‐mediated signaling pathways and antibodies that are available to detect specific TLRs.
Journal ArticleDOI
Reactive Oxygen Species in Inflammation and Tissue Injury
TL;DR: The current review compiles the past and current research in the area of inflammation with particular emphasis on oxidative stress-mediated signaling mechanisms that are involved in inflammation and tissue injury.
Journal ArticleDOI
The immunopathogenesis of sepsis.
TL;DR: Because of the high mortality of sepsis in the face of standard treatment, many efforts have been made to improve understanding of the dysregulation of the host response in sepsi, and much has been learnt of the basic principles governing bacterial–host interactions.
Journal ArticleDOI
LPS/TLR4 signal transduction pathway
TL;DR: Molecules involved in TLR4-mediated signaling are reviewed, including players that are involved in the negative regulation of this important pathway.
Journal ArticleDOI
Innate immune sensing and its roots: the story of endotoxin
Bruce Beutler,Ernst Th Rietschel +1 more
TL;DR: The present concepts grew directly from longstanding efforts to understand infectious disease: how microbes harm the host, what molecules are sensed and, ultimately, the nature of the receptors that the host uses.
References
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Journal ArticleDOI
Innate Immune Recognition
TL;DR: Microbial recognition by Toll-like receptors helps to direct adaptive immune responses to antigens derived from microbial pathogens to distinguish infectious nonself from noninfectious self.
Journal ArticleDOI
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,Christophe Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Silva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,Betsy Layton,Bruce Beutler +13 more
TL;DR: The mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane.
Journal Article
Defective LPS signaling in C3 H/HeJ and C57 BL/10 ScCr mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,C. Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Suva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,B. Layton,Bruce Beutler +13 more
Journal ArticleDOI
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.
Journal ArticleDOI
Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.
K Inaba,M Inaba,Nikolaus Romani,H Aya,Masashi Deguchi,Susumu Ikehara,Shigeru Muramatsu,Ralph M. Steinman +7 more
TL;DR: The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II- negative precursors in marrow, and this feature should prove useful for future molecular and clinical studies of this otherwise trace cell type.