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Toll-Like Receptor Signaling and Its Inducible Proteins
Abstract
Studies that bridge innate immunity and various diseases are making rapid advances. Macrophages and dendritic cells play a leading role in innate immunity, using pattern recognition receptors (PRRs) to sense both pathogen invasion and danger signals. Among these PRRs, the Toll-like receptors (TLRs) play a central role in the immune response by recognizing not only pathogen-associated molecular patterns from bacteria and viruses but also damage-associated molecular patterns from dying or injured cells. These TLR family molecules facilitate not only the elimination of pathogens but also the development of various disorders, including arteriosclerosis, cancer, and metabolic syndrome. TLRs activate signaling pathways that result in the production of cytokines, chemokines, and various inducible molecules associated with the immune response. Although most components of the innate immune signaling pathways, such as the TLR family and its downstream signaling, have been identified, the physiological roles of many TLR signal-inducible proteins remain unclear. Recent studies have shown that some TLR-inducible proteins are critical in the immune response and the development of various disorders. In this review, we focus on the TLR signaling pathways and the roles of some TLR-inducible proteins.
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Cites
Janeway, C. A., & Medzhitov, R. (2002) · Annual Review of Immunology · doi:10.1146/annurev.immunol.20.083001.084359 · Cited by 8,394
Macrophage biology in development, homeostasis and disease
Wynn, T. A., Chawla, A., & Pollard, J. W. (2013) · Nature · doi:10.1038/nature12034 · Cited by 4,684 · cited 1×
“As well as the M1 and M2 macrophages (59 – 62), various functional macrophage/monocyte subtypes have been reported in recent studies that are involved in the development of speci fi c disorders.”
BackgroundMacrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
Seth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005) · Cell · doi:10.1016/j.cell.2005.08.012 · Cited by 3,329
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005) · Nature Immunology · doi:10.1038/ni1243 · Cited by 2,562
Self-citationMonitoring of Blood Vessels and Tissues by a Population of Monocytes with Patrolling Behavior
Auffray, C., Fogg, D., Garfa, M., Elain, G., Join-Lambert, O., Kayal, S., Sarnacki, S., Cumano, A., Lauvau, G., & Geissmann, F. (2007) · Science · doi:10.1126/science.1142883 · Cited by 1,973
Vogl, T., Tenbrock, K., Ludwig, S., Leukert, N., Ehrhardt, C., van Zoelen, M. A. D., Nacken, W., Foell, D., van der Poll, T., Sorg, C., et al. (2007) · Nature Medicine · doi:10.1038/nm1638 · Cited by 1,418 · cited 2×
“In addition to LPS and other bacterial ligands, TLR4 also recognizes S100a8, a ligand derived from dying cells (6, 7).”
BackgroundSatoh, T., Takeuchi, O., Vandenbon, A., Yasuda, K., Tanaka, Y., Kumagai, Y., Miyake, T., Matsushita, K., Okazaki, T., Saitoh, T., et al. (2010) · Nature Immunology · doi:10.1038/ni.1920 · Cited by 1,156
Self-citationHelical Assembly in the MyD88-IRAK4-IRAK2 Complex in TLR/IL-1R Signalling
Lin, S.-C., Lo, Y.-C., & Wu, H. (2010) · Nature · doi:10.1038/nature09121 · Cited by 1,111
CD14 Controls the LPS-Induced Endocytosis of Toll-like Receptor 4
Zanoni, I., Ostuni, R., Marek, L. R., Barresi, S., Barbalat, R., Barton, G. M., Granucci, F., & Kagan, J. C. (2011) · Cell · doi:10.1016/j.cell.2011.09.051 · Cited by 997
Research works printed but not linked: 55
- Akira S Uematsu S Takeuchi O. 2006. Pathogen recognition and innate immunity. Cell 124: 783–801. [PubMed] · DOI · Paper page
- Celhar T Magalhães R Fairhurst AM. 2012. TLR7 and TLR9 in SLE: when sensing self goes wrong. Immunol Res 53: 58–77. [PubMed] · DOI · Paper page
- Kawai T Akira S. 2010. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol 11: 373–384. [PubMed] · DOI · Paper page
- Pouliot P Plante I Raquil MA Tessier PA Olivier M. 2008. Myeloid-related proteins rapidly modulate macrophage nitric oxide production during innate immune response. J Immunol 181: 3595–3601. · DOI
- Suganami T Mieda T Itoh M Shimoda Y Kamei Y Ogawa Y. 2007. Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation. Biochem Biophys Res Commun 354: 45–49. · DOI · Paper page
- Suganami T Tanimoto-Koyama K Nishida J Itoh M Yuan X Mizuarai S Kotani H Yamaoka S Miyake K Aoe S Kamei Y Ogawa Y. 2007. Role of the Toll-like receptor 4/NF-κB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 27: 84–91. [PubMed] · DOI · Paper page
- Kollewe C Mackensen AC Neumann D Knop J Cao P Li S Wesche H Martin MU. 2004. Sequential autophosphorylation steps in the interleukin-1 receptor-associated kinase-1 regulate its availability as an adapter in interleukin-1 signaling. J Biol Chem 279: 5227–5236. · DOI · Paper page
- Jiang Z Ninomiya-Tsuji J Qian Y Matsumoto K Li X. 2002. Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol. Mol Cell Biol 22: 7158–7167. · DOI · Paper page
- Ajibade AA Wang HY Wang RF. 2013. Cell type-specific function of TAK1 in innate immune signaling. Trends Immunol 34: 307–316. [PubMed] · DOI · Paper page
- Chen ZJ. 2012. Ubiquitination in signaling to and activation of IKK. Immunol Rev 246: 95–106. [PubMed] · DOI · Paper page
- Jiang X Chen ZJ. 2011. The role of ubiquitylation in immune defence and pathogen evasion. Nat Rev Immunol 12: 35–48. [PubMed] · DOI · Paper page
- Chang M Jin W Sun SC. 2009. Peli1 facilitates TRIF-dependent Toll-like receptor signaling and proinflammatory cytokine production. Nat Immunol 10: 1089–1095. [PubMed] · DOI · Paper page
- Kawasaki T Takemura N Standley DM Akira S Kawai T. 2013. The second messenger phosphatidylinositol-5-phosphate facilitates antiviral innate immune signaling. Cell Host Microbe 14: 148–158. · DOI
- Blasius AL Beutler B. 2010. Intracellular Toll-like receptors. Immunity 32: 305–315. [PubMed] · DOI · Paper page
- Bernard JJ Cowing-Zitron C Nakatsuji T Muehleisen B Muto J Borkowski AW Martinez L Greidinger EL Yu BD Gallo RL. 2012. Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat Med 18: 1286–1290. [PubMed] · DOI · Paper page
- Takemura N Kawasaki T Kunisawa J Sato S Lamichhane A Kobiyama K Aoshi T Ito J Mizuguchi K Karuppuchamy T Matsunaga K Miyatake S Mori N Tsujimura T Satoh T Kumagai Y Kawai T Standley DM Ishii KJ Kiyono H Akira S Uematsu S. 2014. Blockade of TLR3 protects mice from lethal radiation-induced gastrointestinal syndrome. Nat Commun 5: 3492. doi:10.1038/ncomms4492. · DOI
- Zhang SY Jouanguy E Ugolini S Smahi A Elain G Romero P Segal D Sancho-Shimizu V Lorenzo L Puel A Picard C Chapgier A Plancoulaine S Titeux M Cognet C von Bernuth H Ku CL Casrouge A Zhang XX Barreiro L Leonard J Hamilton C Lebon P Héron B Vallée L Quintana-Murci L Hovnanian A Rozenberg F Vivier E Geissmann F Tardieu M Abel L Casanova JL. 2007. TLR3 deficiency in patients with herpes simplex encephalitis. Science 317: 1522–1527. · DOI · Paper page
- Mancuso G Gambuzza M Midiri A Biondo C Papasergi S Akira S Teti G Beninati C. 2009. Bacterial recognition by TLR7 in the lysosomes of conventional dendritic cells. Nat Immunol 10: 587–594. [PubMed] · DOI · Paper page
- Coban C Igari Y Yagi M Reimer T Koyama S Aoshi T Ohata K Tsukui T Takeshita F Sakurai K Ikegami T Nakagawa A Horii T Nuñez G Ishii KJ Akira S. 2010. Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9. Cell Host Microbe 7: 50–61. · DOI · Paper page
- Tabeta K Hoebe K Janssen EM Du X Georgel P Crozat K Mudd S Mann N Sovath S Goode J Shamel L Herskovits AA Portnoy DA Cooke M Tarantino LM Wiltshire T Steinberg BE Grinstein S Beutler B. 2006. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3 7 and 9. Nat Immunol 7: 156–164. · DOI · Paper page
- Hidmark A von Saint Paul A Dalpke AH. 2012. Cutting edge: TLR13 is a receptor for bacterial RNA. J Immunol 189: 2717–2721. [PubMed] · DOI
- Li XD Chen ZJ. 2012. Sequence specific detection of bacterial 23S ribosomal RNA by TLR13. eLife 1: e00102. doi:10.7554/eLife.00102. [PubMed] · DOI
- Mathur R Oh H Zhang D Park SG Seo J Koblansky A Hayden MS Ghosh S. 2012. A mouse model of Salmonella Typhi infection. Cell 151: 590–602. [PubMed] · DOI · Paper page
- Yarovinsky F Zhang D Andersen JF Bannenberg GL Serhan CN Hayden MS Hieny S Sutterwala FS Flavell RA Ghosh S Sher A. 2005. TLR11 activation of dendritic cells by a protozoan profilin-like protein. Science 308: 1626–1629. · DOI · Paper page
- Koblansky AA Jankovic D Oh H Hieny S Sungnak W Mathur R Hayden MS Akira S Sher A Ghosh S. 2013. Recognition of profilin by Toll-like receptor 12 is critical for host resistance to Toxoplasma gondii . Immunity 38: 119–130. [PubMed] · DOI · Paper page
- Andrade WA Souza MC Ramos-Martinez E Nagpal K Dutra MS Melo MB Bartholomeu DC Ghosh S Golenbock DT Gazzinelli RT. 2013. Combined action of nucleic acid-sensing Toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice. Cell Host Microbe 13: 42–53. · DOI · Paper page
- Broz P Monack DM. 2013. Newly described pattern recognition receptors team up against intracellular pathogens. Nat Rev Immunol 13: 551–565. · DOI · Paper page
- Matsushita K Takeuchi O Standley DM Kumagai Y Kawagoe T Miyake T Satoh T Kato H Tsujimura T Nakamura H Akira S. 2009. Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay. Nature 458: 1185–1190. · DOI · Paper page
- Kayama H Ramirez-Carrozzi VR Yamamoto M Mizutani T Kuwata H Iba H Matsumoto M Honda K Smale ST Takeda K. 2015. Class-specific regulation of pro-inflammatory genes by MyD88 pathways and IκBζ. J Biol Chem 290: 22446. [PubMed] · DOI
- Yamamoto M Yamazaki S Uematsu S Sato S Hemmi H Hoshino K Kaisho T Kuwata H Takeuchi O Takeshige K Saitoh T Yamaoka S Yamamoto N Yamamoto S Muta T Takeda K Akira S. 2004. Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ. Nature 430: 218–222. · DOI · Paper page
- Gilchrist M Thorsson V Li B Rust AG Korb M Roach JC Kennedy K Hai T Bolouri H Aderem A. 2006. Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4. Nature 441: 173–178. [PubMed] · DOI · Paper page
- Bours V Franzoso G Azarenko V Park S Kanno T Brown K Siebenlist U. 1993. The oncoprotein Bcl-3 directly transactivates through κB motifs via association with DNA-binding p50B homodimers. Cell 72: 729–739. · DOI · Paper page
- Kuwata H Matsumoto M Atarashi K Morishita H Hirotani T Koga R Takeda K. 2006. IκBNS inhibits induction of a subset of Toll-like receptor-dependent genes and limits inflammation. Immunity 24: 41–51. [PubMed] · DOI
- Wessells J Baer M Young HA Claudio E Brown K Siebenlist U Johnson PF. 2004. BCL-3 and NF-κB p50 attenuate lipopolysaccharide-induced inflammatory responses in macrophages. J Biol Chem 279: 49995–50003. [PubMed] · DOI · Paper page
- Iwasaki H Takeuchi O Teraguchi S Matsushita K Uehata T Kuniyoshi K Satoh T Saitoh T Matsushita M Standley DM Akira S. 2011. The IκB kinase complex regulates the stability of cytokine-encoding mRNA induced by TLR-IL-1R by controlling degradation of regnase-1. Nat Immunol 12: 1167–1175. · DOI · Paper page
- Uehata T Iwasaki H Vandenbon A Matsushita K Hernandez-Cuellar E Kuniyoshi K Satoh T Mino T Suzuki Y Standley DM Tsujimura T Rakugi H Isaka Y Takeuchi O Akira S. 2013. Malt1-induced cleavage of regnase-1 in CD4 + helper T cells regulates immune activation. Cell 153: 1036–1049. · DOI · Paper page
- Wagner BJ DeMaria CT Sun Y Wilson GM Brewer G. 1998. Structure and genomic organization of the human AUF1 gene: alternative pre-mRNA splicing generates four protein isoforms. Genomics 48: 195–202. [PubMed] · DOI · Paper page
- Carballo E Lai WS Blackshear PJ. 1998. Feedback inhibition of macrophage tumor necrosis factor-α production by tristetraprolin. Science 281: 1001–1005. [PubMed] · DOI · Paper page
- Taylor GA Carballo E Lee DM Lai WS Thompson MJ Patel DD Schenkman DI Gilkeson GS Broxmeyer HE Haynes BF Blackshear PJ. 1996. A pathogenetic role for TNFα in the syndrome of cachexia arthritis and autoimmunity resulting from tristetraprolin (TTP) deficiency. Immunity 4: 445–454. · DOI · Paper page
- Glasmacher E Hoefig KP Vogel KU Rath N Du L Wolf C Kremmer E Wang X Heissmeyer V. 2010. Roquin binds inducible costimulator mRNA and effectors of mRNA decay to induce microRNA-independent post-transcriptional repression. Nat Immunol 11: 725–733. · DOI · Paper page
- Yu D Tan AH Hu X Athanasopoulos V Simpson N Silva DG Hutloff A Giles KM Leedman PJ Lam KP Goodnow CC Vinuesa CG. 2007. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature 450: 299–303. · DOI · Paper page
- Chen CY Gherzi R Ong SE Chan EL Raijmakers R Pruijn GJ Stoecklin G Moroni C Mann M Karin M. 2001. AU binding proteins recruit the exosome to degrade ARE-containing mRNAs. Cell 107: 451–464. [PubMed] · DOI · Paper page
- Gherzi R Lee KY Briata P Wegmüller D Moroni C Karin M Chen CY. 2004. A KH domain RNA binding protein KSRP promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Mol Cell 14: 571–583. [PubMed] · DOI · Paper page
- Agger K Cloos PA Christensen J Pasini D Rose S Rappsilber J Issaeva I Canaani E Salcini AE Helin K. 2007. UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature 449: 731–734. [PubMed] · DOI · Paper page
- Lan F Bayliss PE Rinn JL Whetstine JR Wang JK Chen S Iwase S Alpatov R Issaeva I Canaani E Roberts TM Chang HY Shi Y. 2007. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature 449: 689–694. · DOI · Paper page
- Takeuchi O Akira S. 2010. Pattern recognition receptors and inflammation. Cell 140: 805–820. [PubMed] · DOI · Paper page
- Xu LG Wang YY Han KJ Li LY Zhai Z Shu HB. 2005. VISA is an adapter protein required for virus-triggered IFN-β signaling. Mol Cell 19: 727–740. · DOI · Paper page
- Satoh T Kidoya H Naito H Yamamoto M Takemura N Nakagawa K Yoshioka Y Morii E Takakura N Takeuchi O Akira S. 2013. Critical role of Trib1 in differentiation of tissue-resident M2-like macrophages. Nature 495: 524–528. [PubMed] · DOI · Paper page
- Gordon S Plüddemann A Martinez Estrada F. 2014. Macrophage heterogeneity in tissues: phenotypic diversity and functions. Immunol Rev 262: 36–55. [PubMed] · DOI · Paper page
- Sica A Invernizzi P Mantovani A. 2014. Macrophage plasticity and polarization in liver homeostasis and pathology. Hepatology 59: 2034–2042. [PubMed] · DOI · Paper page
- Asano K Nabeyama A Miyake Y Qiu CH Kurita A Tomura M Kanagawa O Fujii S Tanaka M. 2011. CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity 34: 85–95. [PubMed] · DOI · Paper page
- Carlin LM Stamatiades EG Auffray C Hanna RN Glover L Vizcay-Barrena G Hedrick CC Cook HT Diebold S Geissmann F. 2013. Nr4a1 -dependent Ly6C low monocytes monitor endothelial cells and orchestrate their disposal. Cell 153: 362–375. · DOI · Paper page
- Cheong C Matos I Choi JH Dandamudi DB Shrestha E Longhi MP Jeffrey KL Anthony RM Kluger C Nchinda G Koh H Rodriguez A Idoyaga J Pack M Velinzon K Park CG Steinman RM. 2010. Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209 + dendritic cells for immune T cell areas. Cell 143: 416–429. · DOI · Paper page
- Kumamoto Y Linehan M Weinstein JS Laidlaw BJ Craft JE Iwasaki A. 2013. CD301b + dermal dendritic cells drive T helper 2 cell-mediated immunity. Immunity 39: 733–743. [PubMed] · DOI · Paper page
- Rosas M Davies LC Giles PJ Liao CT Kharfan B Stone TC O’Donnell VB Fraser DJ Jones SA Taylor PR. 2014. The transcription factor Gata6 links tissue macrophage phenotype and proliferative renewal. Science 344: 645–648. · DOI · Paper page
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Metadata
- Authors
- Satoh, T., & Akira, S.
- Venue
- Microbiology Spectrum
- Publisher
- American Society for Microbiology
- Published
- 2016-12-23
- Volume
- 4
- Issue
- 6
- ISSN
- 2165-0497 (ISSN-L)
- OpenAlex
- W2572603768
- Cited by
- 273
- References
- 14
- FWCI
- 9.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- journals.asm.org/non-commercial-tdm-license (tdm)
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