toll like receptors


Summary: A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.

Top Publications

  1. Dasu M, Devaraj S, Park S, Jialal I. Increased toll-like receptor (TLR) activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes Care. 2010;33:861-8 pubmed publisher
  2. Conrad M, Ferstl R, Teich R, Brand S, Blümer N, Yildirim A, et al. Maternal TLR signaling is required for prenatal asthma protection by the nonpathogenic microbe Acinetobacter lwoffii F78. J Exp Med. 2009;206:2869-77 pubmed publisher
    ..lwoffii F78-exposed mothers. These data establish a direct relationship between maternal bacterial exposures, functional maternal TLR signaling, and asthma protection in the progeny. ..
  3. Schikorski D, Cuvillier Hot V, Boidin Wichlacz C, Slomianny C, Salzet M, Tasiemski A. Deciphering the immune function and regulation by a TLR of the cytokine EMAPII in the lesioned central nervous system using a leech model. J Immunol. 2009;183:7119-28 pubmed publisher
  4. Drexler S, Foxwell B. The role of toll-like receptors in chronic inflammation. Int J Biochem Cell Biol. 2010;42:506-18 pubmed publisher
    ..However, future therapies targeting individual TLRs or their signalling transducers may provide a more specific way of treating inflammatory diseases without global suppression of the immune system. ..
  5. Langefeld T, Mohamed W, Ghai R, Chakraborty T. Toll-like receptors and NOD-like receptors: domain architecture and cellular signalling. Adv Exp Med Biol. 2009;653:48-57 pubmed
    ..Here we discuss the common ligand recognition and signalling modules in both these classes of receptors. ..
  6. Woo C, Cui D, Arellano J, Dorweiler B, Harding H, Fitzgerald K, et al. Adaptive suppression of the ATF4-CHOP branch of the unfolded protein response by toll-like receptor signalling. Nat Cell Biol. 2009;11:1473-80 pubmed publisher
    ..We speculate that this mechanism evolved to promote survival of TLR-expressing cells that experience prolonged levels of physiological ER stress in the course of the host response to invading pathogens. ..
  7. Jegalian A, Facchetti F, Jaffe E. Plasmacytoid dendritic cells: physiologic roles and pathologic states. Adv Anat Pathol. 2009;16:392-404 pubmed publisher
    ..Acute leukemia therapy regimens may lead to sustained clinical remission of BPDCN, with bone marrow transplantation in first complete remission potentially curative in adult patients. ..
  8. Ejarque Ortiz A, Gresa Arribas N, Straccia M, Mancera P, Solà C, Tusell J, et al. CCAAT/enhancer binding protein delta in microglial activation. J Neurosci Res. 2010;88:1113-23 pubmed publisher
    ..These results point to C/EBP delta as a putative key regulator of proinflammatory gene expression in microglial activation. ..
  9. Shi Y, Tomic J, Wen F, Shaha S, Bahlo A, Harrison R, et al. Aberrant O-GlcNAcylation characterizes chronic lymphocytic leukemia. Leukemia. 2010;24:1588-98 pubmed publisher
    ..These findings suggest that intracellular O-GlcNAcylation is associated with the pathogenesis of CLL, which could potentially have therapeutic implications. ..

More Information


  1. Peirce M, Brook M, Morrice N, Snelgrove R, Begum S, Lanfrancotti A, et al. Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage Toll-like receptor signaling and cytokine production. PLoS ONE. 2010;5:e11465 pubmed publisher
    ..We hypothesise that Themis2 may constitute a novel, physiological control point in macrophage inflammatory responses. ..
  2. Victoni T, Coelho F, Soares A, de Freitas A, Secher T, Guabiraba R, et al. Local and remote tissue injury upon intestinal ischemia and reperfusion depends on the TLR/MyD88 signaling pathway. Med Microbiol Immunol. 2010;199:35-42 pubmed publisher
    ..In conclusion, our data demonstrate that disruption of the TLR/MyD88 pathway in mice attenuates acute intestinal and lung injury, inflammation, and endothelial damage allowing enhanced survival. ..
  3. Platt A, Bain C, Bordon Y, Sester D, Mowat A. An independent subset of TLR expressing CCR2-dependent macrophages promotes colonic inflammation. J Immunol. 2010;184:6843-54 pubmed publisher
    ..The balance between proinflammatory and resident Ms in the colon is controlled by CCR2-dependent recruitment mechanisms, which could prove useful as targets for therapy in inflammatory bowel disease. ..
  4. Ochiel D, Ghosh M, Fahey J, Guyre P, Wira C. Human uterine epithelial cell secretions regulate dendritic cell differentiation and responses to TLR ligands. J Leukoc Biol. 2010;88:435-44 pubmed publisher
    ..These findings indicate collectively that epithelial cells confer a tolerogenic phenotype to DC in the endometrium. Our results suggest novel cellular and molecular mechanisms for the regulation of adaptive immunity within the FRT. ..
  5. Cario E. Toll-like receptors in inflammatory bowel diseases: a decade later. Inflamm Bowel Dis. 2010;16:1583-97 pubmed publisher
    ..Imbalanced relationships within this triad may promote aberrant TLR signaling, critically contributing to acute and chronic intestinal inflammatory processes in IBD colitis and associated cancer. ..
  6. Evren S, Loai Y, Antoon R, Islam S, Yeger H, Moore K, et al. Urinary bladder tissue engineering using natural scaffolds in a porcine model: role of Toll-like receptors and impact of biomimetic molecules. Cells Tissues Organs. 2010;192:250-61 pubmed publisher
    ..Treatment of grafts with HA and VEGF may help regulate host immune responses by reducing TLR4 and IL-4 and increasing TGF-?1. ..
  7. Enard D, Depaulis F, Roest Crollius H. Human and non-human primate genomes share hotspots of positive selection. PLoS Genet. 2010;6:e1000840 pubmed publisher
    ..The identification of positive selection in humans alongside other primates is a powerful tool to outline those genes that were selected uniquely during recent human evolution. ..
  8. Ramirez J, Dimopoulos G. The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypes. Dev Comp Immunol. 2010;34:625-9 pubmed publisher
    ..These immune defenses are furthermore conserved among different Ae. aegypti strains and can act against a broad range of dengue virus serotypes. ..
  9. Miguel J, Chen J, Van Alstine W, Johnson R. Expression of inflammatory cytokines and Toll-like receptors in the brain and respiratory tract of pigs infected with porcine reproductive and respiratory syndrome virus. Vet Immunol Immunopathol. 2010;135:314-9 pubmed publisher
    ..The findings are interpreted to suggest the innate immune system of the brain is responsive to PRRSV infection. ..
  10. Rodriguez Madoz J, Belicha Villanueva A, Bernal Rubio D, Ashour J, Ayllon J, Fernandez Sesma A. Inhibition of the type I interferon response in human dendritic cells by dengue virus infection requires a catalytically active NS2B3 complex. J Virol. 2010;84:9760-74 pubmed publisher
    ..These results provide a new mechanism by which DENV evades the immune system in humans. ..
  11. Zaffanello M, Malerba G, Cataldi L, Antoniazzi F, Franchini M, Monti E, et al. Genetic risk for recurrent urinary tract infections in humans: a systematic review. J Biomed Biotechnol. 2010;2010:321082 pubmed publisher
    ..In particular, the HSPA1B, CXCR1 & 2, TLR2, TLR4, TGF-beta1 genes seem to be associated with an alteration of the host response to UTIs at various levels. ..
  12. Chakraborty S, Nazmi A, Dutta K, Basu A. Neurons under viral attack: victims or warriors?. Neurochem Int. 2010;56:727-35 pubmed publisher
    ..This article aims to comprehensively analyze current research on this conditional alteration in the protein expression repertoire of neurons and the role it plays in CNS innate immune response to counter viral infections. ..
  13. Gonzalez J, Esteban M. A poxvirus Bcl-2-like gene family involved in regulation of host immune response: sequence similarity and evolutionary history. Virol J. 2010;7:59 pubmed publisher
  14. Caesar R, Fåk F, Backhed F. Effects of gut microbiota on obesity and atherosclerosis via modulation of inflammation and lipid metabolism. J Intern Med. 2010;268:320-8 pubmed publisher
    ..Here, we review how the gut microbiota may affect metabolic diseases by activating the innate immune system. ..
  15. Geng D, Zheng L, Srivastava R, Asprodites N, Velasco Gonzalez C, Davila E. When Toll-like receptor and T-cell receptor signals collide: a mechanism for enhanced CD8 T-cell effector function. Blood. 2010;116:3494-504 pubmed publisher
    ..Furthermore, these findings offer the opportunity for improving the efficacy of vaccines and T cell-based immunotherapies by targeting TLR-MyD88 signaling within T cells. ..
  16. Netzer N, Goodenbour J, David A, Dittmar K, Jones R, Schneider J, et al. Innate immune and chemically triggered oxidative stress modifies translational fidelity. Nature. 2009;462:522-6 pubmed publisher
    ..In demonstrating an unexpected conditional aspect of decoding mRNA, our findings illustrate the importance of considering alternative iterations of the genetic code. ..
  17. Zhang X, Markovic Plese S. Interferon beta inhibits the Th17 cell-mediated autoimmune response in patients with relapsing-remitting multiple sclerosis. Clin Neurol Neurosurg. 2010;112:641-5 pubmed publisher
    ..Our results have identified novel therapeutic mechanisms of IFNbeta, which inhibit Th17 cell differentiation in the context of the autoimmune response in MS. ..
  18. Liu G, Zhang L, Zhao Y. Modulation of immune responses through direct activation of Toll-like receptors to T cells. Clin Exp Immunol. 2010;160:168-75 pubmed publisher
    ..The important effects of TLRs in T cell-intrinsic components also prompt us to explore novel vaccine adjuvants for modifying desired immune responses in an efficient way. ..
  19. Chen K, Malo M, Moss A, Zeller S, Johnson P, Ebrahimi F, et al. Identification of specific targets for the gut mucosal defense factor intestinal alkaline phosphatase. Am J Physiol Gastrointest Liver Physiol. 2010;299:G467-75 pubmed publisher
    ..IAP likely targets these bacterially derived molecules in its role as a gut mucosal defense factor. ..
  20. Hjelm B, Berta A, Nickerson C, Arntzen C, Herbst Kralovetz M. Development and characterization of a three-dimensional organotypic human vaginal epithelial cell model. Biol Reprod. 2010;82:617-27 pubmed publisher
    ..These results indicate that this 3-D vaginal model could be used as a complementary tool for screening microbicide compounds for safety and efficacy, thus improving success in clinical trials. ..
  21. Drewniak A, Tool A, Geissler J, van Bruggen R, van den Berg T, Kuijpers T. Toll-like receptor-induced reactivity and strongly potentiated IL-8 production in granulocytes mobilized for transfusion purposes. Blood. 2010;115:4588-96 pubmed publisher
    ..In summary, granulocytes mobilized for transfusion purposes show enhanced TLR responsiveness in cytokine production, which is anticipated to be beneficial for the function of these cells on transfusion into patients...
  22. McGettrick A, O Neill L. Localisation and trafficking of Toll-like receptors: an important mode of regulation. Curr Opin Immunol. 2010;22:20-7 pubmed publisher
    ..Several proteins, including Triad3A and TAG appear to be involved in the movement of TLR4 to the lysosome for degradation. ..
  23. Spirig R, Djafarzadeh S, Regueira T, Shaw S, von Garnier C, Takala J, et al. Effects of TLR agonists on the hypoxia-regulated transcription factor HIF-1alpha and dendritic cell maturation under normoxic conditions. PLoS ONE. 2010;5:e0010983 pubmed publisher
    ..Current evidence suggests that different target genes may be affected by HIF-1alpha under normoxic conditions with physiological roles that differ from those induced by hypoxia. ..
  24. Gerber J, Nau R. Mechanisms of injury in bacterial meningitis. Curr Opin Neurol. 2010;23:312-8 pubmed publisher
    ..Vasculitis, focal ischemia and brain edema subsequent to an increase in cerebrospinal fluid outflow resistance, breakdown of the blood-brain barrier and swelling of necrotic cells cause secondary brain damage. ..
  25. Gauley J, Pisetsky D. The release of microparticles by RAW 264.7 macrophage cells stimulated with TLR ligands. J Leukoc Biol. 2010;87:1115-23 pubmed publisher
    ..Together, these experiments demonstrate that TLR stimulation of macrophages can lead to MP release, and NO plays a key role in this response. ..
  26. Gluba A, Banach M, Hannam S, Mikhailidis D, Sakowicz A, Rysz J. The role of Toll-like receptors in renal diseases. Nat Rev Nephrol. 2010;6:224-35 pubmed publisher
    ..This Review discusses the evidence supporting a role for TLRs in contrasting bacterial infections and in causing or aggravating renal conditions when TLR activation leads to a harmful inflammatory response. ..
  27. Watts C, West M, Zaru R. TLR signalling regulated antigen presentation in dendritic cells. Curr Opin Immunol. 2010;22:124-30 pubmed publisher
    ..These rapid changes require activation of the MAP kinases, PI3-kinase and downstream signalling pathways and are observed in both myeloid DC and, with variations on the theme, in plasmacytoid DC. ..
  28. Hajishengallis G, Lambris J. Crosstalk pathways between Toll-like receptors and the complement system. Trends Immunol. 2010;31:154-63 pubmed publisher
    ..Further elucidation of regulatory links between complement and TLRs is essential for understanding their complex roles in health and disease. ..
  29. Aboussahoud W, Aflatoonian R, Bruce C, Elliott S, Ward J, Newton S, et al. Expression and function of Toll-like receptors in human endometrial epithelial cell lines. J Reprod Immunol. 2010;84:41-51 pubmed publisher
    ..These results suggest that hTERT-EEC, HEC-1B and Ishikawa cell lines can be used as in vitro models to investigate innate immune responses of endometrial cells in the female reproductive tract. ..
  30. Tanji T, Yun E, Ip Y. Heterodimers of NF-kappaB transcription factors DIF and Relish regulate antimicrobial peptide genes in Drosophila. Proc Natl Acad Sci U S A. 2010;107:14715-20 pubmed publisher
    ..The DIF and Relish complex is detectable in whole animal extracts, suggesting that this heterodimer may function in vivo to increase the spectrum and level of antimicrobial peptide production in response to different infections. ..
  31. Ward C. Pathogen sensing in innate immunity. Expert Rev Vaccines. 2010;9:19-21 pubmed publisher
    ..Eleven talks and six posters were presented; the Chairs gave a detailed introduction, followed by a detailed summation at the end. This article aims to describe the key topics highlighted. ..
  32. Vandevenne P, Sadzot Delvaux C, Piette J. Innate immune response and viral interference strategies developed by human herpesviruses. Biochem Pharmacol. 2010;80:1955-72 pubmed publisher
    ..We will also review the most recent findings in Herpesviruses-encoded proteins involved in host immune evasion. ..
  33. McKernan D, Nolan A, Brint E, O Mahony S, Hyland N, Cryan J, et al. Toll-like receptor mRNA expression is selectively increased in the colonic mucosa of two animal models relevant to irritable bowel syndrome. PLoS ONE. 2009;4:e8226 pubmed publisher
  34. Berthon C, Driss V, Liu J, Kuranda K, Leleu X, Jouy N, et al. In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T cells is induced by TLR ligands and interferon-gamma and can be reversed using MEK inhibitors. Cancer Immunol Immunother. 2010;59:1839-49 pubmed publisher
    ..The efficacy of MEK inhibitors against B7-H1-mediated inhibition of CTLs suggests a possible cancer immunotherapy strategy using targeted drugs. ..
  35. Falcón C, Carranza F, Martínez F, Knubel C, Masih D, Motran C, et al. Excretory-secretory products (ESP) from Fasciola hepatica induce tolerogenic properties in myeloid dendritic cells. Vet Immunol Immunopathol. 2010;137:36-46 pubmed publisher
    ..Our results support the hypothesis that ESP from F. hepatica modulate the maturation and function of DC as part of a generalized immunosuppressive mechanism that involves a bias towards a Th2 response and Treg development. ..
  36. Zhou D, Collins C, Wu P, Brown E. Protein tyrosine phosphatase SHP-1 positively regulates TLR-induced IL-12p40 production in macrophages through inhibition of phosphatidylinositol 3-kinase. J Leukoc Biol. 2010;87:845-55 pubmed publisher
  37. Monroe K, McWhirter S, Vance R. Induction of type I interferons by bacteria. Cell Microbiol. 2010;12:881-90 pubmed publisher
    ..In this review, we discuss recent advances in our understanding of how bacteria induce type I interferons and the roles type I IFNs play in host immunity. ..
  38. Semple J, Freedman J. Platelets and innate immunity. Cell Mol Life Sci. 2010;67:499-511 pubmed publisher
  39. Black M, Trent A, Tirrell M, Olive C. Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists. Expert Rev Vaccines. 2010;9:157-73 pubmed publisher
    ..A survey of recent approaches to developing peptide antigen delivery systems is given, many of which incorporate Toll-like receptor agonists into the design. ..
  40. Finney C, Lu Z, Hawkes M, Yeh W, Liles W, Kain K. Divergent roles of IRAK4-mediated innate immune responses in two experimental models of severe malaria. Am J Trop Med Hyg. 2010;83:69-74 pubmed publisher
  41. Tieri P, Grignolio A, Zaikin A, Mishto M, Remondini D, Castellani G, et al. Network, degeneracy and bow tie. Integrating paradigms and architectures to grasp the complexity of the immune system. Theor Biol Med Model. 2010;7:32 pubmed publisher
    ..e. the capacity to turn an apparently chaotic and highly dynamic set of signals into functional information. ..
  42. Hutchinson M, Loram L, Zhang Y, Shridhar M, Rezvani N, Berkelhammer D, et al. Evidence that tricyclic small molecules may possess toll-like receptor and myeloid differentiation protein 2 activity. Neuroscience. 2010;168:551-63 pubmed publisher
  43. Rosenstiel P, Philipp E, Schreiber S, Bosch T. Evolution and function of innate immune receptors--insights from marine invertebrates. J Innate Immun. 2009;1:291-300 pubmed publisher
    ..e. the animal with all its associated microorganisms, contributes to epithelial homeostasis, immunological integrity and maintenance of the resident microbial diversity. ..
  44. Jermendy A, Korner A, Kovacs M, Kaszas E, Balázsovics J, Szocs A, et al. Association between toll-like receptor polymorphisms and serum levels of tumor necrosis factor-alpha and its soluble receptors in obese children. Med Sci Monit. 2010;16:CR180-185 pubmed
    ..Serum cytokine levels, as modifying factors of insulin resistance, may be affected by TLR4 polymorphisms in obese children. ..
  45. Jagannathan M, Hasturk H, Liang Y, Shin H, Hetzel J, Kantarci A, et al. TLR cross-talk specifically regulates cytokine production by B cells from chronic inflammatory disease patients. J Immunol. 2009;183:7461-70 pubmed publisher
    ..We conclude that disease-associated alteration of B cell TLR responses specifically regulates cytokine production and may influence chronic inflammation. ..
  46. Quesniaux V, Erard F, Ryffel B. Adjuvant activity on murine and human macrophages. Methods Mol Biol. 2010;626:117-30 pubmed publisher
    ..The basic methods to assess macrophage activation are given, which may predict an in vivo activity of a novel adjuvant. ..
  47. Erickson K, Hubbard N. Assessing mucosal immunity with new concepts and innovative, time-honored strategies. Nutr Rev. 2009;67 Suppl 2:S172-82 pubmed publisher
    ..Reviewed here are components of the mucosal immune system with attention paid to the gut-associated lymphoid tissue and some of the new methods for assessing immune responses. ..
  48. Bhattacharyya S, Ratajczak C, Vogt S, Kelley C, Colonna M, Schreiber R, et al. TAK1 targeting by glucocorticoids determines JNK and IkappaB regulation in Toll-like receptor-stimulated macrophages. Blood. 2010;115:1921-31 pubmed publisher
    ..These findings identify TAK1 as a novel target for glucocorticoids that integrates their anti-inflammatory action in innate immunity signaling pathways. ..
  49. Georgel P, Macquin C, Bahram S. The heterogeneous allelic repertoire of human toll-like receptor (TLR) genes. PLoS ONE. 2009;4:e7803 pubmed publisher
    ..Hence this work depicts a first overview of the diversity of almost all human TLR genes, a prelude for large-scale population genetics as well as genetic association studies. ..
  50. Lindsay R, Darrah P, Quinn K, Wille Reece U, Mattei L, Iwasaki A, et al. CD8+ T cell responses following replication-defective adenovirus serotype 5 immunization are dependent on CD11c+ dendritic cells but show redundancy in their requirement of TLR and nucleotide-binding oligomerization domain-like receptor signaling. J Immunol. 2010;185:1513-21 pubmed publisher
    ..Taken together, these data demonstrate a critical role for CD11c(+) DCs for CD8 responses but striking redundancy for innate cytokines and signaling by TLR and nucleotide-binding oligomerization domain-like receptor pathways...
  51. Gong J, Wei T, Zhang N, Jamitzky F, Heckl W, Rossle S, et al. TollML: a database of toll-like receptor structural motifs. J Mol Model. 2010;16:1283-9 pubmed publisher
    ..Additionally, all entries have hyperlinks to various sources including NCBI, Swiss-Prot, PDB, LRRML and PubMed in order to provide broad external information for users. The TollML database is available at ..
  52. Torchinsky M, Garaude J, Blander J. Infection and apoptosis as a combined inflammatory trigger. Curr Opin Immunol. 2010;22:55-62 pubmed publisher
    ..This response is best suited for clearing the infecting pathogen and repairing the damage that occurred to the host tissue during infection. ..
  53. Bloor S, Maelfait J, Krumbach R, Beyaert R, Randow F. Endoplasmic reticulum chaperone gp96 is essential for infection with vesicular stomatitis virus. Proc Natl Acad Sci U S A. 2010;107:6970-5 pubmed publisher
    ..Cells deficient in gp96 also lack functional TLRs, which suggests that pathogen-driven pressure for TLR-mediated immunity maintains the broad host range of VSV-G by positively selecting for the ubiquitous expression of gp96. ..