Open AccessJournal Article
Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product.
Katsuaki Hoshino,Osamu Takeuchi,Taro Kawai,Hideki Sanjo,Tomohiko Ogawa,Yoshifumi Takeda,Kiyoshi Takeda,Shizuo Akira +7 more
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TLDR
It is demonstrated that TLR4 is the gene product that regulates LPS response, and a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family is found.Abstract:
The human homologue of Drosophila Toll (hToll), also called Toll-like receptor 4 (TLR4), is a recently cloned receptor of the IL-1/Toll receptor family. Interestingly, the TLR4 gene has been localized to the same region to which the Lps locus (endotoxin unresponsive gene locus) is mapped. To examine the role of TLR4 in LPS responsiveness, we have generated mice lacking TLR4. Macrophages and B cells from TLR4-deficient mice did not respond to LPS. All these manifestations were quite similar to those of LPS-hyporesponsive C3H/HeJ mice. Furthermore, C3H/HeJ mice have, in the cytoplasmic portion of TLR4, a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family. Overexpression of wild-type TLR4 but not the mutant TLR4 from C3H/HeJ mice activated NF-κB. Taken together, the present study demonstrates that TLR4 is the gene product that regulates LPS response.read more
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Tumor induces muscle wasting in mice through releasing extracellular Hsp70 and Hsp90.
Guohua Zhang,Zhelong Liu,Zhelong Liu,Hui Ding,Hui Ding,Yong Zhou,Hoang Anh Doan,Ka Wai Thomas Sin,Zhiren J. Zhu,René Pedroza Flores,Yefei Wen,Xing Gong,Qingyun Liu,Yi-Ping Li +13 more
TL;DR: It is shown that tumor-released extracellular Hsp70 and Hsp90 are responsible for tumor’s capacity to induce muscle wasting and are identified as key cachexins causing muscle wasting in mice.
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Expression of Toll-like receptor 2 on human Schwann cells: a mechanism of nerve damage in leprosy
Rosane B. de Oliveira,Maria Teresa Ochoa,Peter A. Sieling,Thomas H. Rea,Anura Rambukkana,Euzenir Nunes Sarno,Robert L. Modlin +6 more
TL;DR: The ability of M. leprae ligands to induce the apoptosis of Schwann cells through TLR2 provides a mechanism by which activation of the innate immune response contributes to nerve injury in leprosy.
Journal ArticleDOI
Differential constitutive and cytokine-modulated expression of human Toll-like receptors in primary neutrophils, monocytes, and macrophages.
TL;DR: A potential role for IFN- γ and/or GM-CSF as therapeutic immunomodulators of the host defense to infection is suggested.
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The role of Toll-like receptor 4 in environmental airway injury in mice.
John W. Hollingsworth,Donald N. Cook,David M. Brass,Julia K. L. Walker,Daniel L. Morgan,W. Michael Foster,David A. Schwartz +6 more
TL;DR: It is found that, despite a robust inflammatory response, C57BL/6(TLR4-/-) mice are protected against the development of airway hyperresponsiveness after subchronic ozone exposure.
DNA-containing exosomes derived from cancer cells treated with Topotecan activate a STING-dependent pathway and reinforce antitumor immunity
Yuichi Kitai,Jian Zou,Takuya Sueyoshi,Takumi Kawasaki,Kouji Kobiyama,Ken Ishii,Shizuo Akira,Tadashi Matsuda,Taro Kawai +8 more
TL;DR: It is shown that treatment of breast cancer cells with the antitumor agent topotecan (TPT), an inhibitor of topoisomerase I, induces danger-associated molecular pattern secretion that triggers dendritic cell activation and cytokine production, suggesting that a STING-dependent pathway drives antitumors immunity by responding to tumor cell–derived DNA.
References
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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
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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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The Dorsoventral Regulatory Gene Cassette spätzle/Toll/cactus Controls the Potent Antifungal Response in Drosophila Adults
TL;DR: It is shown that mutations in the Toll signaling pathway dramatically reduce survival after fungal infection and the intracellular components of the dorsoventral signaling pathway and the extracellular Toll ligand, spätzle, control expression of the antifungal peptide gene drosomycin in adults.
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Innate Immunity: The Virtues of a Nonclonal System of Recognition
TL;DR: Characterization of the nonclonal receptors of the innate immune system responsible for the adjuvant activity, and, evidently, for the associated side effects, would provide a powerful alternative approach, which would ultimately allow one to target these receptors directly.