Genomes and Genes
toll like receptor 7
Summary: A pattern recognition receptor that binds several forms of imidazo-quinoline including the antiviral compound Imiquimod.
- Ittah M, Miceli Richard C, Gottenberg J, Sellam J, Lepajolec C, Mariette X. B-cell-activating factor expressions in salivary epithelial cells after dsRNA virus infection depends on RNA-activated protein kinase activation. Eur J Immunol. 2009;39:1271-9 pubmed publisher..Thus, PKR is the dsRNA sensor implicated in BAFF induction in SGEC after dsRNA stimulation. In autoimmune diseases, PKR may be an interesting target for preventing BAFF following the induction of innate immunity. ..
- Weterings J, Khan S, van der Heden van Noort G, Melief C, Overkleeft H, van der Burg S, et al. 2-Azidoalkoxy-7-hydro-8-oxoadenine derivatives as TLR7 agonists inducing dendritic cell maturation. Bioorg Med Chem Lett. 2009;19:2249-51 pubmed publisher..The synthesis of an array of 2-azidoalkoxy substituted 7-hydro-8-oxoadenines is described. The relation of the structure of these compounds and their ability to induce maturation of dendritic cells is evaluated. ..
- Goodchild A, Nopper N, King A, Doan T, Tanudji M, Arndt G, et al. Sequence determinants of innate immune activation by short interfering RNAs. BMC Immunol. 2009;10:40 pubmed publisher..These findings have relevance to the design of siRNAs, particularly for in vivo or clinical applications. ..
- Colisson R, Barblu L, Gras C, Raynaud F, Hadj Slimane R, Pique C, et al. Free HTLV-1 induces TLR7-dependent innate immune response and TRAIL relocalization in killer plasmacytoid dendritic cells. Blood. 2010;115:2177-85 pubmed publisher..This is the first demonstration of an innate immune response induced by free HTLV-1. ..
- Anz D, Koelzer V, Moder S, Thaler R, Schwerd T, Lahl K, et al. Immunostimulatory RNA blocks suppression by regulatory T cells. J Immunol. 2010;184:939-46 pubmed publisher..Thus, we show in this study for the first time that activation of a RIG-I-like helicase on Treg cells blocks their suppressive function. ..
- Palti Y, Gahr S, Purcell M, Hadidi S, Rexroad C, Wiens G. Identification, characterization and genetic mapping of TLR7, TLR8a1 and TLR8a2 genes in rainbow trout (Oncorhynchus mykiss). Dev Comp Immunol. 2010;34:219-33 pubmed publisher..The down-regulation of omTLR8a2 may imply that this gene has evolved to a new or altered function in rainbow trout, as often occurs when the two duplicated genes remain active. ..
- Sonnex C. Toll-like receptors and genital tract infection. Int J STD AIDS. 2010;21:153-7 pubmed publisher..The therapeutic use of TLR agonists as topical agents or for improving CD4+ and CD8+ T-cell responses to microbial vaccines is an important area of ongoing research, particularly with respect to genital mucosal infection. ..
- Rettig L, Haen S, Bittermann A, von Boehmer L, Curioni A, Krämer S, et al. Particle size and activation threshold: a new dimension of danger signaling. Blood. 2010;115:4533-41 pubmed publisher..Our results introduce a new dimension in danger signaling--how size qualitatively affects innate response. ..
- Anguille S, Smits E, Cools N, Goossens H, Berneman Z, Van Tendeloo V. Short-term cultured, interleukin-15 differentiated dendritic cells have potent immunostimulatory properties. J Transl Med. 2009;7:109 pubmed publisher..The results of the present study might pave the way for the implementation of IL-15 DCs in immunotherapy protocols. ..
- Smits E, Cools N, Lion E, Van Camp K, Ponsaerts P, Berneman Z, et al. The Toll-like receptor 7/8 agonist resiquimod greatly increases the immunostimulatory capacity of human acute myeloid leukemia cells. Cancer Immunol Immunother. 2010;59:35-46 pubmed publisher..In conclusion, the immunostimulatory effect of the TLR7/8 agonist R-848 on human AML cells could prove useful for the design of TLR-based immunotherapy for leukemia. ..
- Gollapudi P, Yoon J, Gollapudi S, Pahl M, Vaziri N. Leukocyte toll-like receptor expression in end-stage kidney disease. Am J Nephrol. 2010;31:247-54 pubmed publisher..Monocyte TLR2 and TLR4 and neutrophil TLR4 expressions and TLR4 activity are increased hemodialysis patients, representing another dimension of ESRD-associated inflammation. ..
- Lan T, Dai M, Wang D, Zhu F, Kandimalla E, Agrawal S. Toll-like receptor 7 selective synthetic oligoribonucleotide agonists: synthesis and structure-activity relationship studies. J Med Chem. 2009;52:6871-9 pubmed publisher..In conclusion, we have designed and synthesized novel SIMRA compounds that selectively act as agonists of TLR7. ..
- Quan T, Roman R, Rudenga B, Holers V, Craft J. Epstein-Barr virus promotes interferon-alpha production by plasmacytoid dendritic cells. Arthritis Rheum. 2010;62:1693-701 pubmed publisher..Our results suggest that elevated levels of IFNalpha found in SLE patients may be a result of aberrantly controlled chronic viral infection. ..
- Kurimoto A, Hashimoto K, Nakamura T, Norimura K, Ogita H, Takaku H, et al. Synthesis and biological evaluation of 8-oxoadenine derivatives as toll-like receptor 7 agonists introducing the antedrug concept. J Med Chem. 2010;53:2964-72 pubmed publisher..Therefore, the TLR7 agonist with antedrug characteristics 9e (SM-324405) is a novel candidate for immunotherapy of allergic diseases. ..
- Ward J, West P, Ariaans M, Parker L, Francis S, Crossman D, et al. Temporal interleukin-1beta secretion from primary human peripheral blood monocytes by P2X7-independent and P2X7-dependent mechanisms. J Biol Chem. 2010;285:23147-58 pubmed publisher..Human monocytes released more IL-1beta/cell than macrophages. These data have important implications for inflammatory diseases that involve monocyte activation and IL-1 release. ..
- Gregory S, West J, Dillon P, Hilscher C, Dittmer D, Damania B. Toll-like receptor signaling controls reactivation of KSHV from latency. Proc Natl Acad Sci U S A. 2009;106:11725-30 pubmed publisher..Our findings have broad implications for physiological triggers of latent viral infections, such as herpesviral reactivation and persistence in the host. ..
- Di Domizio J, Blum A, Gallagher Gambarelli M, Molens J, Chaperot L, Plumas J. TLR7 stimulation in human plasmacytoid dendritic cells leads to the induction of early IFN-inducible genes in the absence of type I IFN. Blood. 2009;114:1794-802 pubmed publisher..Thus, pDCs, through this unusual TLR7 signaling, have the capacity to promptly respond to viral infection during the early phases of the innate immune response. ..
- Zhang Y, Guo Y, Bin Li -, Sun S. Hepatitis C virus single-stranded RNA induces innate immunity via Toll-like receptor 7. J Hepatol. 2009;51:29-38 pubmed publisher..These results provide an insight into the development of immune adjuvant for vaccines and for the production of new antiviral drugs. ..
- Kemeny L, Nagy N. [New perspective in immunotherapy: local imiquimod treatment]. Orv Hetil. 2010;151:774-83 pubmed publisher..The drug appears to be well tolerated with mild to moderate to local inflammation at the site of application. This paper provides a review about current experience and possible future development of imiquimod. ..
- Ichinohe T, Pang I, Iwasaki A. Influenza virus activates inflammasomes via its intracellular M2 ion channel. Nat Immunol. 2010;11:404-10 pubmed publisher..Our results show a mechanism by which influenza virus infection activates inflammasomes and identify the sensing of disturbances in intracellular ionic concentrations as a previously unknown pathogen-recognition pathway. ..
- Fukui R, Saitoh S, Matsumoto F, Kozuka Hata H, Oyama M, Tabeta K, et al. Unc93B1 biases Toll-like receptor responses to nucleic acid in dendritic cells toward DNA- but against RNA-sensing. J Exp Med. 2009;206:1339-50 pubmed publisher..Consistently, the D34A mutation up-regulated ligand-induced trafficking of TLR7 but down-regulated that of TLR9. Collectively, TLR response to nucleic acids in DCs is biased toward DNA-sensing by Unc93B1. ..
- Lukacs N, Smit J, Mukherjee S, Morris S, Nunez G, Lindell D. Respiratory virus-induced TLR7 activation controls IL-17-associated increased mucus via IL-23 regulation. J Immunol. 2010;185:2231-9 pubmed publisher..Thus, without TLR7-mediated responses, an altered immune environment ensued with a significant effect on airway epithelial cell remodeling and goblet cell hyper/metaplasia, leading to increased mucus production...
- Clarke S, Laxton C, Horscroft N, Richard V, Thomas A, Parkinson T. Comparison of rat and human responses to toll-like receptor 7 activation. J Interferon Cytokine Res. 2009;29:113-26 pubmed publisher..We conclude that rat and human cells respond differently to TLR7 activation and that these differences should be considered when using rat as a model to study TLR7 agonists. ..
- Zhan Y, Xu Y, Seah S, Brady J, Carrington E, Cheers C, et al. Resident and monocyte-derived dendritic cells become dominant IL-12 producers under different conditions and signaling pathways. J Immunol. 2010;185:2125-33 pubmed publisher..In contrast, for mDC, IL-12 production was mainly dependent on MyD88 signaling. Thus, conventional DCs and mDCs use different pathways to regulate IL-12 production. ..
- Morozumi T, Uenishi H. Polymorphism distribution and structural conservation in RNA-sensing Toll-like receptors 3, 7, and 8 in pigs. Biochim Biophys Acta. 2009;1790:267-74 pubmed publisher..Recognition of virus-derived RNA is critical in host defense against infection. These results should provide a useful clue to analysis of the association between polymorphisms in RNA-sensing TLRs and disease resistance. ..
- Cros J, Cagnard N, Woollard K, Patey N, Zhang S, Senechal B, et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity. 2010;33:375-86 pubmed publisher..Thus, CD14(dim) cells are bona fide monocytes involved in the innate local surveillance of tissues and the pathogenesis of autoimmune diseases. ..
- Johnson T, Rao S, Seder R, Chen M, Graham B. TLR9 agonist, but not TLR7/8, functions as an adjuvant to diminish FI-RSV vaccine-enhanced disease, while either agonist used as therapy during primary RSV infection increases disease severity. Vaccine. 2009;27:3045-52 pubmed publisher..Furthermore, these data underscore that amplification of anti-viral immune responses may result in immunopathology rather than immune-mediated protection. ..
- Nickerson K, Christensen S, Shupe J, Kashgarian M, Kim D, Elkon K, et al. TLR9 regulates TLR7- and MyD88-dependent autoantibody production and disease in a murine model of lupus. J Immunol. 2010;184:1840-8 pubmed publisher..These results suggest new models for how Tlr9 regulates and Tlr7 enhances disease and provide insight into aspects of autoimmune disease that are, and are not, influenced by TLR signals. ..
- Ma F, Zhang J, Zhang J, Zhang C. The TLR7 agonists imiquimod and gardiquimod improve DC-based immunotherapy for melanoma in mice. Cell Mol Immunol. 2010;7:381-8 pubmed publisher..More importantly, they can be used as vaccine adjuvants to potentiate the efficiency of DC-based tumor immunotherapy. ..
- Dharmapuri S, Aurisicchio L, Neuner P, Verdirame M, Ciliberto G, La Monica N. An oral TLR7 agonist is a potent adjuvant of DNA vaccination in transgenic mouse tumor models. Cancer Gene Ther. 2009;16:462-72 pubmed publisher..These observations therefore emphasize the potential of SM360320 as immunological adjuvant for therapeutic DNA vaccines. ..
- Xirakia C, Koltsida O, Stavropoulos A, Thanassopoulou A, Aidinis V, Sideras P, et al. Toll-like receptor 7-triggered immune response in the lung mediates acute and long-lasting suppression of experimental asthma. Am J Respir Crit Care Med. 2010;181:1207-16 pubmed publisher..This provides important insight into the efficacy and mode of action of TLR7 ligands in murine models of allergic airway disease and paves the way for their clinical application in humans. ..
- Wenink M, Santegoets K, Broen J, van Bon L, Abdollahi Roodsaz S, Popa C, et al. TLR2 promotes Th2/Th17 responses via TLR4 and TLR7/8 by abrogating the type I IFN amplification loop. J Immunol. 2009;183:6960-70 pubmed publisher..This shift in T cell responses was inherent to the inability of TLR2-stimulated DCs to produce IL-12p70 and was dependent on the production of IL-1 and IL-6. ..
- Forward N, Furlong S, Yang Y, Lin T, Hoskin D. Signaling through TLR7 enhances the immunosuppressive activity of murine CD4+CD25+ T regulatory cells. J Leukoc Biol. 2010;87:117-25 pubmed publisher..We speculate that TLR7-stimulated enhancement of T(reg) cell suppressor function may modulate host T cell responses against ssRNA viruses. ..
- Shukla N, Kimbrell M, Malladi S, David S. Regioisomerism-dependent TLR7 agonism and antagonism in an imidazoquinoline. Bioorg Med Chem Lett. 2009;19:2211-4 pubmed publisher..A des-amino precursor of the 3H regioisomer is more potent as a TLR7 antagonist, with an IC(50) value of 7.5 microM. This class of compound may serve as a starting point for the development of small-molecule inhibitors of TLR7. ..
- Sanchez E, Callejas Rubio J, Sabio J, Gonzalez Gay M, Jimenez Alonso J, Mico L, et al. Investigation of TLR5 and TLR7 as candidate genes for susceptibility to systemic lupus erythematosus. Clin Exp Rheumatol. 2009;27:267-71 pubmed..08). These results suggest that the tested variations of TLR5 and TLR7 genes do not confer a relevant role in the susceptibility or severity to SLE in the Spanish population. ..
- Adams S, O Neill D, Nonaka D, Hardin E, Chiriboga L, Siu K, et al. Immunization of malignant melanoma patients with full-length NY-ESO-1 protein using TLR7 agonist imiquimod as vaccine adjuvant. J Immunol. 2008;181:776-84 pubmed..Imiquimod's adjuvant effects require further evaluation and likely need optimization of parameters such as formulation, dose, and timing relative to Ag exposure for maximal immunogenicity. ..
- Younesi V, Nikzamir H, Yousefi M, Khoshnoodi J, Arjmand M, Rabbani H, et al. Epstein Barr virus inhibits the stimulatory effect of TLR7/8 and TLR9 agonists but not CD40 ligand in human B lymphocytes. Microbiol Immunol. 2010;54:534-41 pubmed publisher..EBV infection did not induce apoptosis and did not downregulate TLR7/8 mRNA expression in B lymphocytes. Our results suggest that EBV might be able to evade the immune system by modulation of the TLR signaling pathway...
- Sioud M. Development of TLR7/8 small RNA antagonists. Methods Mol Biol. 2010;629:387-94 pubmed publisher..This chapter describes the characterization of immunosuppressive RNA oligonucleotides carrying 2'-modified uridines. ..
- Gill M, Bajwa G, George T, Dong C, Dougherty I, Jiang N, et al. Counterregulation between the FcepsilonRI pathway and antiviral responses in human plasmacytoid dendritic cells. J Immunol. 2010;184:5999-6006 pubmed publisher..These data suggest that counterregulation of FcepsilonRI and TLR-7 pathways exists in pDCs, and that IgE cross-linking impairs pDC antiviral responses. ..
- Vanden Bush T, Buchta C, Claudio J, Bishop G. Cutting Edge: Importance of IL-6 and cooperation between innate and adaptive immune receptors in cellular vaccination with B lymphocytes. J Immunol. 2009;183:4833-7 pubmed publisher..These findings reveal alternative stimulation strategies for the production of effective Bvac and identify a key role for IL-6 in B cell Ag presentation and cellular vaccines. ..
- Stary G, Klein I, Kohlhofer S, Koszik F, Scherzer T, Müllauer L, et al. Plasmacytoid dendritic cells express TRAIL and induce CD4+ T-cell apoptosis in HIV-1 viremic patients. Blood. 2009;114:3854-63 pubmed publisher..Definition of pDCs as killers of CD4+ T cells implies a new mechanism of disease progression in HIV infection. ..
- Eberle F, Sirin M, Binder M, Dalpke A. Bacterial RNA is recognized by different sets of immunoreceptors. Eur J Immunol. 2009;39:2537-47 pubmed publisher..Our results show that besides of activation of TLR7 and inflammasomes, bacterial RNA activates additional cytosolic receptors similarly as has been reported for recognition of bacterial DNA. ..
- Huang S, Wei W, Yun Y. Upregulation of TLR7 and TLR3 gene expression in the lung of respiratory syncytial virus infected mice. Wei Sheng Wu Xue Bao. 2009;49:239-45 pubmed..This may allow to detect viral infections and initiate a proinflammatory response via multiple TLRs. This study may be useful in the development of tools to modulate the activities of therapeutic TLR ligands. ..