Book ChapterDOI
Signal transduction pathways activated by the IL-1 receptor/toll-like receptor superfamily.
TLDR
Differences between signals generated by TLRs are emerging, with TLR-4 signalling requiring an additional adapter termed MyD88-adapter-like (Mal), which may regulate the expression of genes specific for the response required to eliminate infection by Gram-negative bacteria.Abstract:
Toll-like receptors (TLRs) are an important point of first contact between host and microbe, and once activated generate signals which culminate in the induction of genes important for host defence. TLRs respond to different microbial products, and the signalling pathways activated are very similar to that generated by the pro-inflammatory cytokine interleukin-1 (IL-1). This is because the Type I IL-1 receptor and TLRs are highly homologous in their cytosolic portions, possessing a Toll/IL-1 receptor (TIR) domain. Signals triggered include the important transcription factor NF-кB and two MAP kinases, p38 and Jun N-terminal kinase. Receptor-proximal proteins involved include the adapter MyD88, IRAK, IRAK-2, Tollip, TRAF6 and TAK-1. These latter two proteins need to be ubiquitinated in order to be active. Differences between signals generated by TLRs are emerging, with TLR-4 signalling requiring an additional adapter termed MyD88-adapter-like (Mal), which may regulate the expression of genes specific for the response required to eliminate infection by Gram-negative bacteria. Future studies on TLR signalling may reveal hitherto unsuspected specificities in the innate immune response to infection.read more
Citations
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Journal ArticleDOI
Toll-like receptor signaling.
TL;DR: Current understanding of the TLR signaling pathways is reviewed, which shows that individual TLRs can activate overlapping as well as distinct signaling pathways, ultimately giving rise to distinct biological effects.
Journal ArticleDOI
Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein.
Jong Sung Park,Daiva Svetkauskaite,Qianbin He,Jae-Yeol Kim,Derek Strassheim,Akitoshi Ishizaka,Edward Abraham +6 more
TL;DR: Interactions ofHMGB1 with TLR 2 and TLR 4 may provide an explanation for the ability of HMGB1 to generate inflammatory responses that are similar to those initiated by LPS.
Journal ArticleDOI
Pyogenic Bacterial Infections in Humans with MyD88 Deficiency
Horst von Bernuth,Capucine Picard,Capucine Picard,Zhongbo Jin,Rungnapa Pankla,Rungnapa Pankla,Hui Xiao,Cheng-Lung Ku,Cheng-Lung Ku,Maya Chrabieh,Maya Chrabieh,Imen Ben Mustapha,Imen Ben Mustapha,Imen Ben Mustapha,Pegah Ghandil,Pegah Ghandil,Yildiz Camcioglu,Júlia Vasconcelos,Nicolas Sirvent,Margarida Guedes,Artur Bonito Vitor,María José Herrero-Mata,Juan I. Aróstegui,Carlos Rodrigo,Laia Alsina,Estibaliz Ruiz-Ortiz,Manel Juan,Claudia Fortuny,Jordi Yagüe,Jordi Anton,Mariona Pascal,Huey Hsuan Chang,Lucile Janniere,Lucile Janniere,Yoann Rose,Yoann Rose,Ben Zion Garty,Helen Chapel,Andrew C. Issekutz,László Maródi,Carlos Rodríguez-Gallego,Jacques Banchereau,Laurent Abel,Laurent Abel,Xiaoxia Li,Damien Chaussabel,Anne Puel,Anne Puel,Jean-Laurent Casanova,Jean-Laurent Casanova +49 more
TL;DR: Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease, but these patients were otherwise healthy, with normal resistance to other microbes.
Journal ArticleDOI
Comparative Analysis of the Receptor-Like Kinase Family in Arabidopsis and Rice
Shin-Han Shiu,Wojciech M. Karlowski,Runsun Pan,Runsun Pan,Yun-Huei Tzeng,Yun-Huei Tzeng,Klaus F. X. Mayer,Wen-Hsiung Li +7 more
TL;DR: It is found that rice (Oryza sativa) has nearly twice as many RLK/Pelle members as Arabidopsis does, and it is not simply a consequence of a larger predicted gene number in rice.
Journal ArticleDOI
HMGB1 signals through toll-like receptor (TLR) 4 and TLR2.
Man Yu,Haichao Wang,Aihao Ding,Douglas T. Golenbock,Eicke Latz,Christopher J. Czura,Matthew J. Fenton,Kevin J. Tracey,Huan Yang +8 more
TL;DR: It is demonstrated that in human whole blood, neutralizing antibodies against Toll-like receptor 4 (TLR4, but not TLR2 or receptor for advanced glycation end product) dose-dependently attenuate HMGB1-induced IL-8 release, suggesting that there is a differential usage ofTLR2 and TLR4 inHMGB1 signaling in primary cells and in established cell lines.
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
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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 Toll-like receptor recognizes bacterial DNA.
Hiroaki Hemmi,Osamu Takeuchi,Taro Kawai,Tsuneyasu Kaisho,Shintaro Sato,Hideki Sanjo,Makoto Matsumoto,Katsuaki Hoshino,Hermann Wagner,Kiyoshi Takeda,Shizuo Akira +10 more
TL;DR: It is shown that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9, and vertebrate immune systems appear to have evolved a specific Toll- like receptor that distinguishes bacterial DNA from self-DNA.
Journal ArticleDOI
Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3.
TL;DR: It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs).
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.