toll like receptor 8


Summary: A pattern recognition receptor that recognizes GUANOSINE and URIDINE-rich single-stranded RNA.

Top Publications

  1. Hurst J, Prinz N, Lorenz M, Bauer S, Chapman J, Lackner K, et al. TLR7 and TLR8 ligands and antiphospholipid antibodies show synergistic effects on the induction of IL-1beta and caspase-1 in monocytes and dendritic cells. Immunobiology. 2009;214:683-91 pubmed publisher
    ..APL seem to enforce this process hinting that endogenous stimulation of TLRs in the Antiphospholipid Syndrome (APS) patients resulted in enhanced secretion of proinflammatory cytokines. ..
  2. Ablasser A, Poeck H, Anz D, Berger M, Schlee M, Kim S, et al. Selection of molecular structure and delivery of RNA oligonucleotides to activate TLR7 versus TLR8 and to induce high amounts of IL-12p70 in primary human monocytes. J Immunol. 2009;182:6824-33 pubmed publisher
  3. Zhang P, Cox C, Alvarez K, Cunningham M. Cutting edge: cardiac myosin activates innate immune responses through TLRs. J Immunol. 2009;183:27-31 pubmed publisher
    ..Our data suggest that cardiac myosin and its pathogenic T cell epitopes may link innate and adaptive immunity in a novel mechanism that could promote chronic inflammation in the myocardium. ..
  4. 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. ..
  5. Saruta M, Michelsen K, Thomas L, Yu Q, Landers C, Targan S. TLR8-mediated activation of human monocytes inhibits TL1A expression. Eur J Immunol. 2009;39:2195-202 pubmed publisher
    ..Our data demonstrate for the first time a direct interaction between TLR and TL1A signaling pathways. TLR8 activation may be an important, novel pathway for targeted treatment of Th1-mediated diseases, such as CD. ..
  6. Lombardi V, Van Overtvelt L, Horiot S, Moingeon P. Human dendritic cells stimulated via TLR7 and/or TLR8 induce the sequential production of Il-10, IFN-gamma, and IL-17A by naive CD4+ T cells. J Immunol. 2009;182:3372-9 pubmed publisher
    ..The observed polymorphism in DC responses to such TLR-mediated stimuli could explain differences in the susceptibility to infectious pathogens or autoimmune diseases within the human population. ..
  7. Döring Y, Hurst J, Lorenz M, Prinz N, Clemens N, Drechsler M, et al. Human antiphospholipid antibodies induce TNFalpha in monocytes via Toll-like receptor 8. Immunobiology. 2010;215:230-41 pubmed publisher
    ..This could be confirmed in PBMC's of APS patients, hinting that endogenous stimulation of TLR8 in APS patients and consecutive elevation of TNFalpha promotes a proinflammatory environment. ..
  8. 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. ..
  9. Gantier M, Irving A, Kaparakis Liaskos M, Xu D, Evans V, Cameron P, et al. Genetic modulation of TLR8 response following bacterial phagocytosis. Hum Mutat. 2010;31:1069-79 pubmed publisher
    ..Thus, TLR8 sensing can be activated following bacterial phagocytosis, and rs3764880 may play a role in the modulation of TLR8-dependent microbicidal response of infected macrophages. ..

More Information


  1. Soulika A, Lee E, McCauley E, Miers L, Bannerman P, Pleasure D. Initiation and progression of axonopathy in experimental autoimmune encephalomyelitis. J Neurosci. 2009;29:14965-79 pubmed publisher
  2. Adepoju L, Geiger J. Antitumor activity of polyuridylic acid in human soft tissue and bone sarcomas. J Surg Res. 2010;164:e107-14 pubmed publisher
    ..These results elucidate the effect of PolyU in STS and BS cells and demonstrate that PolyU may be a potential therapeutic agent for STS and BS. ..
  3. 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. ..
  4. 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. ..
  5. 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. ..
  6. Toka F, Nfon C, Dawson H, Golde W. Accessory-cell-mediated activation of porcine NK cells by toll-like receptor 7 (TLR7) and TLR8 agonists. Clin Vaccine Immunol. 2009;16:866-78 pubmed publisher
  7. Gantier M, Tong S, Behlke M, Irving A, Lappas M, Nilsson U, et al. Rational design of immunostimulatory siRNAs. Mol Ther. 2010;18:785-95 pubmed publisher
    ..Our data suggest that this sequence modification coupled with structural modification differentially recruits human TLR8 over TLR7, and could have potential application in antiviral therapies. ..
  8. Yanagisawa S, Koarai A, Sugiura H, Ichikawa T, Kanda M, Tanaka R, et al. Oxidative stress augments toll-like receptor 8 mediated neutrophilic responses in healthy subjects. Respir Res. 2009;10:50 pubmed publisher
    ..These results suggest that oxidative stress might potentiate the neutrophilic inflammation during viral infection. ..
  9. Nicholas S, Sumbayev V. The role of redox-dependent mechanisms in the downregulation of ligand-induced Toll-like receptors 7, 8 and 4-mediated HIF-1 alpha prolyl hydroxylation. Immunol Cell Biol. 2010;88:180-6 pubmed publisher
    ..In both cases, downregulation of HIF-1 alpha prolyl hydroxylation correlates with a decrease in intracellular iron (II). ..
  10. 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. ..
  11. Robbins M, Judge A, MacLachlan I. siRNA and innate immunity. Oligonucleotides. 2009;19:89-102 pubmed publisher
  12. 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. ..
  13. Sioud M. Deciphering the code of innate immunity recognition of siRNAs. Methods Mol Biol. 2009;487:41-59 pubmed publisher
  14. 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...
  15. Cherfils Vicini J, Platonova S, Gillard M, Laurans L, Validire P, Caliandro R, et al. Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance. J Clin Invest. 2010;120:1285-97 pubmed publisher
  16. Skjaeveland I, Iliev D, Strandskog G, J rgensen J. Identification and characterization of TLR8 and MyD88 homologs in Atlantic salmon (Salmo salar). Dev Comp Immunol. 2009;33:1011-7 pubmed publisher
    ..Furthermore, ectopic expression of SsMyD88 in HEK cells was able to activate a NF-kappaB reporter construct indicating that the cloned salmon molecule was a functional MyD88 homologue...
  17. Guo Y, Zhao G, Tanaka S, Yamaguchi T. Differential responses between monocytes and monocyte-derived macrophages for lipopolysaccharide stimulation of calves. Cell Mol Immunol. 2009;6:223-9 pubmed publisher
    ..Besides, no expression of TLR9 was found. As antigen presenting cells, monocytes and monocyte-derived macrophages respond differently to LPS, so they may have different functions in the innate immune system. ..
  18. Nicholas S, Sumbayev V. The involvement of hypoxia-inducible factor 1 alpha in Toll-like receptor 7/8-mediated inflammatory response. Cell Res. 2009;19:973-83 pubmed publisher
    ..Thus, HIF-1alpha might support both cell survival and the production of pro-inflammatory cytokines upon TLR7/8 activation. ..
  19. Mäkelä S, Strengell M, Pietila T, Osterlund P, Julkunen I. Multiple signaling pathways contribute to synergistic TLR ligand-dependent cytokine gene expression in human monocyte-derived macrophages and dendritic cells. J Leukoc Biol. 2009;85:664-72 pubmed publisher
    ..Our data suggest that TLR-dependent, synergistic cytokine gene expression results from enhanced activation and cooperation among NF-kappaB, IRF, MAPK, PI-3K, and STAT signaling pathways. ..
  20. Demaria O, Pagni P, Traub S, de Gassart A, Branzk N, Murphy A, et al. TLR8 deficiency leads to autoimmunity in mice. J Clin Invest. 2010;120:3651-62 pubmed publisher
    ..These data provide evidence for a pivotal role for mouse TLR8 in the regulation of mouse TLR7 expression and prevention of spontaneous autoimmunity. ..
  21. Butchar J, Mehta P, Justiniano S, Guenterberg K, Kondadasula S, Mo X, et al. Reciprocal regulation of activating and inhibitory Fc{gamma} receptors by TLR7/8 activation: implications for tumor immunotherapy. Clin Cancer Res. 2010;16:2065-75 pubmed publisher
    ..These results show an as-yet-undiscovered regulatory and functional link between the TLR7/8 and FcgammaR pathways. This suggests that TLR7/8 agonists may be especially beneficial during antibody therapy. ..
  22. Ganguly D, Chamilos G, Lande R, Gregorio J, Meller S, Facchinetti V, et al. Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. J Exp Med. 2009;206:1983-94 pubmed publisher
    ..Our results demonstrate that the cationic antimicrobial peptide LL37 converts self-RNA into a trigger of TLR7 and TLR8 in human DCs, and provide new insights into the mechanism that drives the auto-inflammatory responses in psoriasis. ..
  23. Gantier M, Williams B. Monitoring innate immune recruitment by siRNAs in mammalian cells. Methods Mol Biol. 2010;623:21-33 pubmed publisher
    ..This chapter provides a brief overview of the current knowledge of siRNA-induced innate immunity, as well as protocols for the rapid identification of siRNAs with innate immune stimulatory activity. ..
  24. Du J, Wu Z, Ren S, Wei Y, Gao M, Randolph G, et al. TLR8 agonists stimulate newly recruited monocyte-derived cells into potent APCs that enhance HBsAg immunogenicity. Vaccine. 2010;28:6273-81 pubmed publisher
    ..These results suggest that TLR8 agonists are good candidates to enhance recombinant HBsAg immunogenicity to induce specific humoral and cellular immune responses...
  25. Biasin M, Piacentini L, Lo Caputo S, Naddeo V, Pierotti P, Borelli M, et al. TLR activation pathways in HIV-1-exposed seronegative individuals. J Immunol. 2010;184:2710-7 pubmed publisher
  26. Tluk S, Jurk M, Forsbach A, Weeratna R, Samulowitz U, Krieg A, et al. Sequences derived from self-RNA containing certain natural modifications act as suppressors of RNA-mediated inflammatory immune responses. Int Immunol. 2009;21:607-19 pubmed publisher
    ..This knowledge can be used to include as few as a single 2'-O-methyl modification at a specific position in a siRNA sense or anti-sense strand to avoid TLR immune effects. ..
  27. Zhou Y, Ye L, Wan Q, Zhou L, Wang X, Li J, et al. Activation of Toll-like receptors inhibits herpes simplex virus-1 infection of human neuronal cells. J Neurosci Res. 2009;87:2916-25 pubmed publisher
    ..These observations indicate that human neuronal cells possess intracellular TLR-mediated innate immune protection against HSV-1 infection. ..
  28. Wei T, Gong J, Jamitzky F, Heckl W, Stark R, Rossle S. Homology modeling of human Toll-like receptors TLR7, 8, and 9 ligand-binding domains. Protein Sci. 2009;18:1684-91 pubmed publisher
    ..We suggest further investigations of these residues through mutation experiments. Our modeling approach can be extended to other members of the TLR family or other repetitive proteins. ..
  29. Astakhova N, Perelygin A, Zharkikh A, Lear T, Coleman S, MacLeod J, et al. Characterization of equine and other vertebrate TLR3, TLR7, and TLR8 genes. Immunogenetics. 2009;61:529-39 pubmed publisher
    ..A phylogenetic analysis did not indicate that any significant exchanges had occurred between paralogous TLR7 and TLR8 genes in 20 vertebrate species analyzed...
  30. Wurzenberger C, Koelzer V, Schreiber S, Anz D, Vollmar A, Schnurr M, et al. Short-term activation induces multifunctional dendritic cells that generate potent antitumor T-cell responses in vivo. Cancer Immunol Immunother. 2009;58:901-13 pubmed publisher
    ..Thus, short-term activation of DC generates fully functional DC for tumor immunotherapy. These results may guide the design of new protocols for DC generation in order to develop more efficient DC-based tumor vaccines. ..
  31. Larangé A, Antonios D, Pallardy M, Kerdine Romer S. TLR7 and TLR8 agonists trigger different signaling pathways for human dendritic cell maturation. J Leukoc Biol. 2009;85:673-83 pubmed publisher
    ..This study showed that TLR7 and TLR8 activate similar signaling pathways that play different roles in DC maturation, depending on which TLR is triggered. ..
  32. Spranger S, Javorovic M, Bürdek M, Wilde S, Mosetter B, Tippmer S, et al. Generation of Th1-polarizing dendritic cells using the TLR7/8 agonist CL075. J Immunol. 2010;185:738-47 pubmed publisher
    ..Thereby, mature DCs prepared within 3 d using such maturation mixtures displayed optimal functions required for vaccine development. ..
  33. Dillon S, Rogers L, Howe R, Hostetler L, Buhrman J, McCarter M, et al. Human intestinal lamina propria CD1c+ dendritic cells display an activated phenotype at steady state and produce IL-23 in response to TLR7/8 stimulation. J Immunol. 2010;184:6612-21 pubmed publisher
    ..These findings highlight a potential mechanism by which viruses like HIV-1 may subvert homeostatic mechanisms and induce inflammation in the intestinal mucosa. ..
  34. Hamm S, Rath S, Michel S, Baumgartner R. Cancer immunotherapeutic potential of novel small molecule TLR7 and TLR8 agonists. J Immunotoxicol. 2009;6:257-65 pubmed publisher
    ..Therefore, a compound that activates both TLR7 and TLR8 would result in a highly efficient immune system activation and may give rise to an enhanced anti-tumor activity in vivo compared to that elicited by a monospecific TLR7 agonist. ..
  35. Clancy R, Alvarez D, Komissarova E, Barrat F, Swartz J, Buyon J. Ro60-associated single-stranded RNA links inflammation with fetal cardiac fibrosis via ligation of TLRs: a novel pathway to autoimmune-associated heart block. J Immunol. 2010;184:2148-55 pubmed publisher
  36. Liu J, Xu C, Hsu L, Luo Y, Xiang R, Chuang T. A five-amino-acid motif in the undefined region of the TLR8 ectodomain is required for species-specific ligand recognition. Mol Immunol. 2010;47:1083-90 pubmed publisher
    ..Deletion mutation analysis suggested that this motif is essential for the species-specific ligand recognition of hTLR8, whereas it is not required for self-dimerization and intracellular localization of this receptor. ..
  37. Vanden Bush T, Bishop G. TLR7 and CD40 cooperate in IL-6 production via enhanced JNK and AP-1 activation. Eur J Immunol. 2008;38:400-9 pubmed publisher
    ..In addition, the dual stimulation increased cFos/AP-1 species in stimulated cells, effectively expanding the repertoire of AP-1 dimers as compared to singly stimulated B cells. ..
  38. Chang B, Cross J, Najar H, Dutz J. Topical resiquimod promotes priming of CTL to parenteral antigens. Vaccine. 2009;27:5791-9 pubmed publisher
    ..Topical resiquimod is a potent adjuvant for locally administered subcutaneous vaccines, inducing clinically relevant CTL responses following single application at the time of subcutaneous vaccination. ..
  39. Chen Z, Ma G, Qian Q, Yao Y, Feng Y, Tang C. Toll-like receptor 8 polymorphism and coronary artery disease. Mol Biol Rep. 2009;36:1897-901 pubmed publisher
    ..No associations existed between these two SNPs and the severity of coronary artery stenosis (All P > 0.05). These results do not support an involvement of SNPs rs3764879 and rs3764880 of TLR8 in predisposition to CAD. ..
  40. Wang D, Precopio M, Lan T, Yu D, Tang J, Kandimalla E, et al. Antitumor activity and immune response induction of a dual agonist of Toll-like receptors 7 and 8. Mol Cancer Ther. 2010;9:1788-97 pubmed publisher
    ..CL25 pulmonary metastasis model. These studies show that the dual TLR7/8 agonist induced Th1-type immune responses and potent antitumor activity in mice via TLR7 and through the MyD88-dependent pathway. ..
  41. Vanderwerf S, Svahn J, Olson S, Rathbun R, Harrington C, Yates J, et al. TLR8-dependent TNF-(alpha) overexpression in Fanconi anemia group C cells. Blood. 2009;114:5290-8 pubmed publisher
    ..In conclusion, FANCC suppresses TNF-alpha production in mononuclear phagocytes by suppressing TLR8 activity and this particular function of FANCC is independent of its function in protecting the genome from cross-linking agents. ..
  42. 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. ..
  43. Janke M, Poth J, Wimmenauer V, Giese T, Coch C, Barchet W, et al. Selective and direct activation of human neutrophils but not eosinophils by Toll-like receptor 8. J Allergy Clin Immunol. 2009;123:1026-33 pubmed publisher
  44. Bessa J, Kopf M, Bachmann M. Cutting edge: IL-21 and TLR signaling regulate germinal center responses in a B cell-intrinsic manner. J Immunol. 2010;184:4615-9 pubmed publisher
    ..Hence, IL-21 acts directly on B cells and cooperates with TLR signaling for optimal B cell responses. ..
  45. Lan T, Putta M, Wang D, Dai M, Yu D, Kandimalla E, et al. Synthetic oligoribonucleotides-containing secondary structures act as agonists of Toll-like receptors 7 and 8. Biochem Biophys Res Commun. 2009;386:443-8 pubmed publisher
    ..These results suggest that secondary structures in ORN provide nuclease stability and lead to stimulation of immune responses through TLR8 as well as TLR7 depending on the presence of specific nucleotide motifs. ..
  46. Klechevsky E, Flamar A, Cao Y, Blanck J, Liu M, O Bar A, et al. Cross-priming CD8+ T cells by targeting antigens to human dendritic cells through DCIR. Blood. 2010;116:1685-97 pubmed publisher
    ..Thus, antigen targeting via the human DCIR receptor allows activation of specific CD8(+) T-cell immunity. ..
  47. Berger M, Ablasser A, Kim S, Bekeredjian Ding I, Giese T, Endres S, et al. TLR8-driven IL-12-dependent reciprocal and synergistic activation of NK cells and monocytes by immunostimulatory RNA. J Immunother. 2009;32:262-71 pubmed publisher
  48. 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. ..
  49. Kuka M, Baronio R, Valentini S, Monaci E, Muzzi A, Aprea S, et al. Src kinases are required for a balanced production of IL-12/IL-23 in human dendritic cells activated by Toll-like receptor agonists. PLoS ONE. 2010;5:e11491 pubmed publisher
    ..We suggest that the pharmacological modulation of DC maturation has the potential to shape the quality of the adaptive immune response and could be exploited for the treatment of inflammation-related diseases. ..
  50. Zhang W, Du X, Zhao G, Jin H, Kang Y, Xiao C, et al. Levamisole is a potential facilitator for the activation of Th1 responses of the subunit HBV vaccination. Vaccine. 2009;27:4938-46 pubmed publisher
  51. Ben Yebdri F, Kukulski F, Tremblay A, Sevigny J. Concomitant activation of P2Y(2) and P2Y(6) receptors on monocytes is required for TLR1/2-induced neutrophil migration by regulating IL-8 secretion. Eur J Immunol. 2009;39:2885-94 pubmed publisher
    ..In line with our previous work on TLR4, this study further supports the importance of nucleotides in bacterial-induced neutrophil migration. ..
  52. Chaung H, Chen C, Hsieh B, Chung W. Toll-Like Receptor expressions in porcine alveolar macrophages and Dendritic Cells in responding to poly IC stimulation and porcine reproductive and respiratory syndrome virus (PRRSV) infection. Comp Immunol Microbiol Infect Dis. 2010;33:197-213 pubmed publisher
    ..Hence, the differential TLR expression patterns in porcine AMs and DCs in discrimination of the imitated viral dsRNA or PRRSV infection may determine their cytokine expressions and thus affect the resulting immune responses...
  53. Zannetti C, Bonnay F, Takeshita F, Parroche P, Menetrier Caux C, Tommasino M, et al. C/EBP{delta} and STAT-1 are required for TLR8 transcriptional activity. J Biol Chem. 2010;285:34773-80 pubmed publisher
    ..These results shed new light on the mechanisms involved during TLR8-mediated innate immune response. ..