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Toll-like receptors (TLRs) and immune disorders

  • REVIEW ARTICLE
  • Published:
Journal of Infection and Chemotherapy

Abstract

Upon the invasion of pathogens, the immune system needs to mount defense responses immediately. Over the past 10 years, Toll-like receptors (TLRs) have been discovered in mammals and defined as pathogen sensors. TLRs are considered to bind directly to ligands, discriminate them immediately, and induce defense responses when appropriate. We here review microbial recognition by TLRs, downstream signaling, and the relationship of TLRs to susceptibility to infectious diseases and immune disorders. Recent reports have revealed a requirement for co-receptors in TLR responses. A TLR signaling pathway is required for protection against infectious diseases, but excessive signaling may lead to allergies, autoimmune diseases, or atherosclerosis. In humans, several deficiencies of signaling molecules downstream of TLRs, and TLR polymorphisms that affect recognition or signaling, were reported to cause immunodeficiencies. It is important to understand how TLR signaling is controlled.

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References

  1. S Gerttula YS Jin KV Anderson (1988) ArticleTitleZygotic expression and activity of the Drosophila Toll gene, a gene required maternally for embryonic dorsal-ventral pattern formation Genetics 119 123–33 Occurrence Handle2456252 Occurrence Handle1:STN:280:BieB1cvivFw%3D

    PubMed  CAS  Google Scholar 

  2. C Hashimoto KL Hudson KV Anderson (1988) ArticleTitleThe Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein Cell 52 269–79 Occurrence Handle2449285 Occurrence Handle1:CAS:528:DyaL1MXitVKrtrc%3D Occurrence Handle10.1016/0092-8674(88)90516-8

    Article  PubMed  CAS  Google Scholar 

  3. B Lemaitre E Nicolas L Michaut JM Reichhart JA Hoffmann (1996) ArticleTitleThe dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults Cell 86 973–83 Occurrence Handle8808632 Occurrence Handle1:CAS:528:DyaK28XlvV2nsLY%3D Occurrence Handle10.1016/S0092-8674(00)80172-5

    Article  PubMed  CAS  Google Scholar 

  4. R Medzhitov P Preston-Hurlburt CA Janeway SuffixJr (1997) ArticleTitleA human homologue of the Drosophila Toll protein signals activation of adaptive immunity Nature 388 394–7 Occurrence Handle9237759 Occurrence Handle1:CAS:528:DyaK2sXkvVChurc%3D Occurrence Handle10.1038/41131

    Article  PubMed  CAS  Google Scholar 

  5. U Hasan C Chaffois C Gaillard V Saulnier E Merck S Tancredi et al. (2005) ArticleTitleHuman TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88 J Immunol 174 2942–50 Occurrence Handle15728506 Occurrence Handle1:CAS:528:DC%2BD2MXhsFeqsbc%3D

    PubMed  CAS  Google Scholar 

  6. D Zhang G Zhang MS Hayden MB Greenblatt C Bussey RA Flavell et al. (2004) ArticleTitleA toll-like receptor that prevents infection by uropathogenic bacteria Science 303 1522–6 Occurrence Handle15001781 Occurrence Handle1:CAS:528:DC%2BD2cXhslCgsLY%3D Occurrence Handle10.1126/science.1094351

    Article  PubMed  CAS  Google Scholar 

  7. B Kobe AV Kajava (2001) ArticleTitleThe leucine-rich repeat as a protein recognition motif Curr Opin Struct Biol 11 725–32 Occurrence Handle11751054 Occurrence Handle1:CAS:528:DC%2BD3MXpt1aqsL8%3D Occurrence Handle10.1016/S0959-440X(01)00266-4

    Article  PubMed  CAS  Google Scholar 

  8. JK Bell I Botos PR Hall J Askins J Shiloach DM Segal et al. (2005) ArticleTitleThe molecular structure of the Toll-like receptor 3 ligand-binding domain Proc Natl Acad Sci U S A 102 10 976–80 Occurrence Handle1:CAS:528:DC%2BD2MXnvVWjur4%3D

    CAS  Google Scholar 

  9. JK Bell GE Mullen CA Leifer A Mazzoni DR Davies DM Segal (2003) ArticleTitleLeucine-rich repeats and pathogen recognition in Toll-like receptors Trends Immunol 24 528–33 Occurrence Handle14552836 Occurrence Handle1:CAS:528:DC%2BD3sXnvVKktLg%3D Occurrence Handle10.1016/S1471-4906(03)00242-4

    Article  PubMed  CAS  Google Scholar 

  10. J Choe MS Kelker IA Wilson (2005) ArticleTitleCrystal structure of human toll-like receptor 3 (TLR3) ectodomain Science 309 581–5 Occurrence Handle15961631 Occurrence Handle1:CAS:528:DC%2BD2MXmsFChtro%3D Occurrence Handle10.1126/science.1115253

    Article  PubMed  CAS  Google Scholar 

  11. F Yarovinsky D Zhang JF Andersen GL Bannenberg CN Serhan MS Hayden et al. (2005) ArticleTitleTLR11 activation of dendritic cells by a protozoan profilin-like protein Science 308 1626–9 Occurrence Handle15860593 Occurrence Handle1:CAS:528:DC%2BD2MXltFemsLo%3D Occurrence Handle10.1126/science.1109893

    Article  PubMed  CAS  Google Scholar 

  12. K Takeda S Akira (2003) ArticleTitleToll receptors and pathogen resistance Cell Microbiol 5 143–53 Occurrence Handle12614458 Occurrence Handle1:CAS:528:DC%2BD3sXisVejsbk%3D Occurrence Handle10.1046/j.1462-5822.2003.00264.x

    Article  PubMed  CAS  Google Scholar 

  13. O Takeuchi S Sato T Horiuchi K Hoshino K Takeda Z Dong et al. (2002) ArticleTitleCutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins J Immunol 169 10–4 Occurrence Handle12077222 Occurrence Handle1:CAS:528:DC%2BD38XltVKjtbs%3D

    PubMed  CAS  Google Scholar 

  14. DM Klinman (2004) ArticleTitleImmunotherapeutic uses of CpG oligodeoxynucleotides Nat Rev Immunol 4 249–58 Occurrence Handle15057783 Occurrence Handle1:CAS:528:DC%2BD2cXis1GksLk%3D Occurrence Handle10.1038/nri1329

    Article  PubMed  CAS  Google Scholar 

  15. S Saitoh S Akashi T Yamada N Tanimura M Kobayashi K Konno et al. (2004) ArticleTitleLipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization Int Immunol 16 961–9 Occurrence Handle15184344 Occurrence Handle1:CAS:528:DC%2BD2cXltVWnt74%3D Occurrence Handle10.1093/intimm/dxh097

    Article  PubMed  CAS  Google Scholar 

  16. K Kawasaki S Akashi R Shimazu T Yoshida K Miyake M Nishijima (2000) ArticleTitleMouse toll-like receptor 4.MD-2 complex mediates lipopolysaccharide-mimetic signal transduction by Taxol J Biol Chem 275 2251–4 Occurrence Handle10644670 Occurrence Handle1:CAS:528:DC%2BD3cXpvFertg%3D%3D Occurrence Handle10.1074/jbc.275.4.2251

    Article  PubMed  CAS  Google Scholar 

  17. EA Kurt-Jones L Popova L Kwinn LM Haynes LP Jones RA Tripp et al. (2000) ArticleTitlePattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus Nat Immunol 1 398–401 Occurrence Handle11062499 Occurrence Handle1:CAS:528:DC%2BD3cXnvVGht78%3D Occurrence Handle10.1038/80833

    Article  PubMed  CAS  Google Scholar 

  18. Y Okamura M Watari ES Jerud DW Young ST Ishizaka J Rose et al. (2001) ArticleTitleThe extra domain A of fibronectin activates Toll-like receptor 4 J Biol Chem 276 10 229–33 Occurrence Handle1:CAS:528:DC%2BD3MXis1Okt78%3D Occurrence Handle10.1074/jbc.M100099200

    Article  CAS  Google Scholar 

  19. K Ohashi V Burkart S Flohe H Kolb (2000) ArticleTitleCutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex J Immunol 164 558–61 Occurrence Handle10623794 Occurrence Handle1:CAS:528:DC%2BD3cXlt1ChtA%3D%3D

    PubMed  CAS  Google Scholar 

  20. C Habich K Baumgart H Kolb V Burkart (2002) ArticleTitleThe receptor for heat shock protein 60 on macrophages is saturable, specific, and distinct from receptors for other heat shock proteins J Immunol 168 569–76 Occurrence Handle11777948 Occurrence Handle1:CAS:528:DC%2BD38XksFWntA%3D%3D

    PubMed  CAS  Google Scholar 

  21. C Termeer F Benedix J Sleeman C Fieber U Voith T Ahrens et al. (2002) ArticleTitleOligosaccharides of hyaluronan activate dendritic cells via toll-like receptor 4 J Exp Med 195 99–111 Occurrence Handle11781369 Occurrence Handle1:CAS:528:DC%2BD38XjslOjtw%3D%3D Occurrence Handle10.1084/jem.20001858

    Article  PubMed  CAS  Google Scholar 

  22. S Viriyakosol PS Tobias RL Kitchens TN Kirkland (2001) ArticleTitleMD-2 binds to bacterial lipopolysaccharide J Biol Chem 276 38 044–51 Occurrence Handle1:CAS:528:DC%2BD3MXotFOrtbY%3D

    CAS  Google Scholar 

  23. S Akashi Y Nagai H Ogata M Oikawa K Fukase S Kusumoto et al. (2001) ArticleTitleHuman MD-2 confers on mouse Toll-like receptor 4 species-specific lipopolysaccharide recognition Int Immunol 13 1595–9 Occurrence Handle11717200 Occurrence Handle1:CAS:528:DC%2BD3MXptVKmt7Y%3D Occurrence Handle10.1093/intimm/13.12.1595

    Article  PubMed  CAS  Google Scholar 

  24. M Kobayashi S Saitoh N Tanimura K Takahashi K Kawasaki M Nishijima et al. (2006) ArticleTitleRegulatory roles for MD-2 and TLR4 in ligand-induced receptor clustering J Immunol 176 6211–8 Occurrence Handle16670331 Occurrence Handle1:CAS:528:DC%2BD28XktVWgu7c%3D

    PubMed  CAS  Google Scholar 

  25. Y Nagai S Akashi M Nagafuku M Ogata Y Iwakura S Akira et al. (2002) ArticleTitleEssential role of MD-2 in LPS responsiveness and TLR4 distribution Nat Immunol 3 667–72 Occurrence Handle12055629 Occurrence Handle1:CAS:528:DC%2BD38Xksl2mur8%3D

    PubMed  CAS  Google Scholar 

  26. J Pugin S Stern-Voeffray B Daubeuf MA Matthay G Elson I Dunn-Siegrist (2004) ArticleTitleSoluble MD-2 activity in plasma from patients with severe sepsis and septic shock Blood 104 4071–9 Occurrence Handle15328161 Occurrence Handle1:CAS:528:DC%2BD2cXhtFaju7nK Occurrence Handle10.1182/blood-2003-04-1290

    Article  PubMed  CAS  Google Scholar 

  27. Z Jiang P Georgel X Du L Shamel S Sovath S Mudd et al. (2005) ArticleTitleCD14 is required for MyD88-independent LPS signaling Nat Immunol 6 565–70 Occurrence Handle15895089 Occurrence Handle1:CAS:528:DC%2BD2MXktlWit7o%3D Occurrence Handle10.1038/ni1207

    Article  PubMed  CAS  Google Scholar 

  28. LM Stuart J Deng JM Silver K Takahashi AA Tseng EJ Hennessy et al. (2005) ArticleTitleResponse to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain J Cell Biol 170 477–85 Occurrence Handle16061696 Occurrence Handle1:CAS:528:DC%2BD2MXntVarsrw%3D Occurrence Handle10.1083/jcb.200501113

    Article  PubMed  CAS  Google Scholar 

  29. K Hoebe P Georgel S Rutschmann X Du S Mudd K Crozat et al. (2005) ArticleTitleCD36 is a sensor of diacylglycerides Nature 433 523–7 Occurrence Handle15690042 Occurrence Handle1:CAS:528:DC%2BD2MXpt1Clsw%3D%3D Occurrence Handle10.1038/nature03253

    Article  PubMed  CAS  Google Scholar 

  30. K Tabeta K Hoebe EM Janssen X Du P Georgel K Crozat et al. (2006) ArticleTitleThe Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9 Nat Immunol 7 156–64 Occurrence Handle16415873 Occurrence Handle1:CAS:528:DC%2BD28Xlt1ersA%3D%3D Occurrence Handle10.1038/ni1297

    Article  PubMed  CAS  Google Scholar 

  31. Y Nagai T Kobayashi Y Motoi K Ishiguro S Akashi S Saitoh et al. (2005) ArticleTitleThe radioprotective 105/MD-1 complex links TLR2 and TLR4/MD-2 in antibody response to microbial membranes J Immunol 174 7043–9 Occurrence Handle15905547 Occurrence Handle1:CAS:528:DC%2BD2MXkt1Omtbo%3D

    PubMed  CAS  Google Scholar 

  32. S Divanovic A Trompette SF Atabani R Madan DT Golenbock A Visintin et al. (2005) ArticleTitleNegative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105 Nat Immunol 6 571–8 Occurrence Handle15852007 Occurrence Handle1:CAS:528:DC%2BD2MXktlWitrg%3D Occurrence Handle10.1038/ni1198

    Article  PubMed  CAS  Google Scholar 

  33. S Koarada Y Tada O Ushiyama F Morito N Suzuki A Ohta et al. (1999) ArticleTitleB cells lacking RP105, a novel B cell antigen, in systemic lupus erythematosus Arthritis Rheum 42 2593–600 Occurrence Handle10616005 Occurrence Handle1:CAS:528:DC%2BD3cXjslansQ%3D%3D Occurrence Handle10.1002/1529-0131(199912)42:12<2593::AID-ANR12>3.0.CO;2-G

    Article  PubMed  CAS  Google Scholar 

  34. S Koarada M Ide Y Haruta Y Tada O Ushiyama F Morito et al. (2005) ArticleTitleTwo cases of antinuclear antibody negative lupus showing increased proportion of B cells lacking RP105 J Rheumatol 32 562–4 Occurrence Handle15742454

    PubMed  Google Scholar 

  35. T Horng GM Barton R Medzhitov (2001) ArticleTitleTIRAP: an adapter molecule in the Toll signaling pathway Nat Immunol 2 835–41 Occurrence Handle11526399 Occurrence Handle1:CAS:528:DC%2BD3MXmsFehtrc%3D Occurrence Handle10.1038/ni0901-835

    Article  PubMed  CAS  Google Scholar 

  36. KA Fitzgerald EM Palsson-McDermott AG Bowie CA Jefferies AS Mansell G Brady et al. (2001) ArticleTitleMal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction Nature 413 78–83 Occurrence Handle11544529 Occurrence Handle1:CAS:528:DC%2BD3MXmvFSrsrg%3D Occurrence Handle10.1038/35092578

    Article  PubMed  CAS  Google Scholar 

  37. M Yamamoto S Sato K Mori K Hoshino O Takeuchi K Takeda et al. (2002) ArticleTitleCutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling J Immunol 169 6668–72 Occurrence Handle12471095 Occurrence Handle1:CAS:528:DC%2BD38XpsFCqu74%3D

    PubMed  CAS  Google Scholar 

  38. M Yamamoto S Sato H Hemmi S Uematsu K Hoshino T Kaisho et al. (2003) ArticleTitleTRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway Nat Immunol 4 1144–50 Occurrence Handle14556004 Occurrence Handle1:CAS:528:DC%2BD3sXosVyktb8%3D Occurrence Handle10.1038/ni986

    Article  PubMed  CAS  Google Scholar 

  39. G Oganesyan SK Saha B Guo JQ He A Shahangian B Zarnegar et al. (2006) ArticleTitleCritical role of TRAF3 in the Toll-like receptor-dependent and -independent antiviral response Nature 439 208–11 Occurrence Handle16306936 Occurrence Handle1:CAS:528:DC%2BD28XislKhtQ%3D%3D Occurrence Handle10.1038/nature04374

    Article  PubMed  CAS  Google Scholar 

  40. AF McGettrick LA O'Neill (2004) ArticleTitleThe expanding family of MyD88-like adaptors in Toll-like receptor signal transduction Mol Immunol 41 577–82 Occurrence Handle15219996 Occurrence Handle1:CAS:528:DC%2BD2cXltFOns74%3D Occurrence Handle10.1016/j.molimm.2004.04.006

    Article  PubMed  CAS  Google Scholar 

  41. M Schnare GM Barton AC Holt K Takeda S Akira R Medzhitov (2001) ArticleTitleToll-like receptors control activation of adaptive immune responses Nat Immunol 2 947–50 Occurrence Handle11547333 Occurrence Handle1:CAS:528:DC%2BD3MXnsVCis74%3D Occurrence Handle10.1038/ni712

    Article  PubMed  CAS  Google Scholar 

  42. JN Kline K Kitagaki TR Businga VV Jain (2002) ArticleTitleTreatment of established asthma in a murine model using CpG oligodeoxy nucleotides Am J Physiol Lung Cell Mol Physiol 283 L170–9 Occurrence Handle12060574 Occurrence Handle1:CAS:528:DC%2BD38XlsVCqsr4%3D

    PubMed  CAS  Google Scholar 

  43. K Gerhold K Blumchen A Bock C Seib P Stock T Kallinich et al. (2002) ArticleTitleEndotoxins prevent murine IgE production, T(H)2 immune responses, and development of airway eosinophilia but not airway hyperreactivity J Allergy Clin Immunol 110 110–6 Occurrence Handle12110829 Occurrence Handle1:CAS:528:DC%2BD38Xmt1Wkt7Y%3D Occurrence Handle10.1067/mai.2002.125831

    Article  PubMed  CAS  Google Scholar 

  44. SC Eisenbarth DA Piggott JW Huleatt I Visintin CA Herrick K Bottomly (2002) ArticleTitleLipopolysaccharide-enhanced, toll-like receptor 4-dependent T helper cell type 2 responses to inhaled antigen J Exp Med 196 1645–51 Occurrence Handle12486107 Occurrence Handle1:CAS:528:DC%2BD38XpslWlu7g%3D Occurrence Handle10.1084/jem.20021340

    Article  PubMed  CAS  Google Scholar 

  45. TR Hawn KD Smith A Aderem SJ Skerrett (2006) ArticleTitleMyeloid differentiation primary response gene (88)- and Toll-like receptor 2-deficient mice are susceptible to infection with aerosolized Legionella pneumophila J Infect Dis 193 1693–702 Occurrence Handle16703513 Occurrence Handle1:CAS:528:DC%2BD28XmtlGrtLY%3D Occurrence Handle10.1086/504525

    Article  PubMed  CAS  Google Scholar 

  46. KA Archer CR Roy (2006) ArticleTitleMyD88-dependent responses involving Toll-like receptor 2 are important for protection and clearance of Legionella pneumophila in a mouse model of Legionnaires' disease Infect Immun 74 3325–33 Occurrence Handle16714560 Occurrence Handle1:CAS:528:DC%2BD28Xlt1Cgur0%3D Occurrence Handle10.1128/IAI.02049-05

    Article  PubMed  CAS  Google Scholar 

  47. CM Greene TP Carroll SG Smith CC Taggart J Devaney S Griffin et al. (2005) ArticleTitleTLR-induced inflammation in cystic fibrosis and non-cystic fibrosis airway epithelial cells J Immunol 174 1638–46 Occurrence Handle15661927 Occurrence Handle1:CAS:528:DC%2BD2MXlsFyluw%3D%3D

    PubMed  CAS  Google Scholar 

  48. N Liu RR Montgomery SW Barthold LK Bockenstedt (2004) ArticleTitleMyeloid differentiation antigen 88 deficiency impairs pathogen clearance but does not alter inflammation in Borrelia burgdorferi-infected mice Infect Immun 72 3195–203 Occurrence Handle15155621 Occurrence Handle1:CAS:528:DC%2BD2cXkslCiu78%3D Occurrence Handle10.1128/IAI.72.6.3195-3203.2004

    Article  PubMed  CAS  Google Scholar 

  49. DD Bolz RS Sundsbak Y Ma S Akira CJ Kirschning JF Zachary et al. (2004) ArticleTitleMyD88 plays a unique role in host defense but not arthritis development in Lyme disease J Immunol 173 2003–10 Occurrence Handle15265935 Occurrence Handle1:CAS:528:DC%2BD2cXlvVajtrc%3D

    PubMed  CAS  Google Scholar 

  50. S Bellocchio C Montagnoli S Bozza R Gaziano G Rossi SS Mambula et al. (2004) ArticleTitleThe contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo J Immunol 172 3059–69 Occurrence Handle14978111 Occurrence Handle1:CAS:528:DC%2BD2cXhsVCrtb0%3D

    PubMed  CAS  Google Scholar 

  51. EA Leadbetter IR Rifkin AM Hohlbaum BC Beaudette MJ Shlomchik A Marshak-Rothstein (2002) ArticleTitleChromatin-IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors Nature 416 603–7 Occurrence Handle11948342 Occurrence Handle1:CAS:528:DC%2BD38XjtFahur8%3D Occurrence Handle10.1038/416603a

    Article  PubMed  CAS  Google Scholar 

  52. M Ehlers H Fukuyama TL McGaha A Aderem JV Ravetch (2006) ArticleTitleTLR9/MyD88 signaling is required for class switching to pathogenic IgG2a and 2b autoantibodies in SLE J Exp Med 203 553–61 Occurrence Handle16492804 Occurrence Handle1:CAS:528:DC%2BD28XjsVSqtb8%3D Occurrence Handle10.1084/jem.20052438

    Article  PubMed  CAS  Google Scholar 

  53. H Bjorkbacka VV Kunjathoor KJ Moore S Koehn CM Ordija MA Lee et al. (2004) ArticleTitleReduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways Nat Med 10 416–21 Occurrence Handle15034566 Occurrence Handle10.1038/nm1008

    Article  PubMed  Google Scholar 

  54. KS Michelsen MH Wong PK Shah W Zhang J Yano TM Doherty et al. (2004) ArticleTitleLack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E Proc Natl Acad Sci U S A 101 10 679–84 Occurrence Handle1:CAS:528:DC%2BD2cXmtFWmtr0%3D Occurrence Handle10.1073/pnas.0403249101

    Article  CAS  Google Scholar 

  55. J Stack IR Haga M Schroder NW Bartlett G Maloney PC Reading et al. (2005) ArticleTitleVaccinia virus protein A46R targets multiple Toll-like-interleukin-1 receptor adaptors and contributes to virulence J Exp Med 201 1007–18 Occurrence Handle15767367 Occurrence Handle1:CAS:528:DC%2BD2MXislOhu7c%3D Occurrence Handle10.1084/jem.20041442

    Article  PubMed  CAS  Google Scholar 

  56. K Li E Foy JC Ferreon M Nakamura AC Ferreon M Ikeda et al. (2005) ArticleTitleImmune evasion by hepatitis C virus NS3/4A protease-mediated cleavage of the Toll-like receptor 3 adaptor protein TRIF Proc Natl Acad Sci U S A 102 2992–7 Occurrence Handle15710891 Occurrence Handle1:CAS:528:DC%2BD2MXitVSkt7g%3D Occurrence Handle10.1073/pnas.0408824102

    Article  PubMed  CAS  Google Scholar 

  57. S Uematsu S Sato M Yamamoto T Hirotani H Kato F Takeshita et al. (2005) ArticleTitleInterleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction J Exp Med 201 915–23 Occurrence Handle15767370 Occurrence Handle1:CAS:528:DC%2BD2MXislOhu78%3D Occurrence Handle10.1084/jem.20042372

    Article  PubMed  CAS  Google Scholar 

  58. T Kawai S Sato KJ Ishii C Coban H Hemmi M Yamamoto et al. (2004) ArticleTitleInterferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6 Nat Immunol 5 1061–8 Occurrence Handle15361868 Occurrence Handle1:CAS:528:DC%2BD2cXnvFCgs7w%3D Occurrence Handle10.1038/ni1118

    Article  PubMed  CAS  Google Scholar 

  59. K Honda H Yanai H Negishi M Asagiri M Sato T Mizutani et al. (2005) ArticleTitleIRF-7 is the master regulator of type-I interferon-dependent immune responses Nature 434 772–7 Occurrence Handle15800576 Occurrence Handle1:CAS:528:DC%2BD2MXivFCgurg%3D Occurrence Handle10.1038/nature03464

    Article  PubMed  CAS  Google Scholar 

  60. A Takaoka H Yanai S Kondo G Duncan H Negishi T Mizutani et al. (2005) ArticleTitleIntegral role of IRF-5 in the gene induction programme activated by Toll-like receptors Nature 434 243–9 Occurrence Handle15665823 Occurrence Handle1:CAS:528:DC%2BD2MXitV2iu7g%3D Occurrence Handle10.1038/nature03308

    Article  PubMed  CAS  Google Scholar 

  61. Z Jiang HJ Johnson H Nie J Qin TA Bird X Li (2003) ArticleTitlePellino 1 is required for interleukin-1 (IL-1)-mediated signaling through its interaction with the IL-1 receptor-associated kinase 4 (IRAK4)-IRAK-tumor necrosis factor receptor-associated factor 6 (TRAF6) complex J Biol Chem 278 10 952–6 Occurrence Handle1:CAS:528:DC%2BD3sXit1Khu70%3D

    CAS  Google Scholar 

  62. J Qin Z Jiang Y Qian JL Casanova X Li (2004) ArticleTitleIRAK4 kinase activity is redundant for interleukin-1 (IL-1) receptor-associated kinase phosphorylation and IL-1 responsiveness J Biol Chem 279 26748–53 Occurrence Handle15084582 Occurrence Handle1:CAS:528:DC%2BD2cXkvVWgtb8%3D Occurrence Handle10.1074/jbc.M400785200

    Article  PubMed  CAS  Google Scholar 

  63. N Day N Tangsinmankong H Ochs R Rucker C Picard JL Casanova et al. (2004) ArticleTitleInterleukin receptor-associated kinase (IRAK-4) deficiency associated with bacterial infections and failure to sustain antibody responses J Pediatr 144 524–6 Occurrence Handle15069404 Occurrence Handle10.1016/j.jpeds.2003.11.025

    Article  PubMed  Google Scholar 

  64. C Picard A Puel M Bonnet CL Ku J Bustamante K Yang et al. (2003) ArticleTitlePyogenic bacterial infections in humans with IRAK-4 deficiency Science 299 2076–9 Occurrence Handle12637671 Occurrence Handle1:CAS:528:DC%2BD3sXitlCisLo%3D Occurrence Handle10.1126/science.1081902

    Article  PubMed  CAS  Google Scholar 

  65. AE Medvedev A Lentschat DB Kuhns JC Blanco C Salkowski S Zhang et al. (2003) ArticleTitleDistinct mutations in IRAK-4 confer hyporesponsiveness to lipopolysaccharide and interleukin-1 in a patient with recurrent bacterial infections J Exp Med 198 521–31 Occurrence Handle12925671 Occurrence Handle1:CAS:528:DC%2BD3sXms1Wis7g%3D Occurrence Handle10.1084/jem.20030701

    Article  PubMed  CAS  Google Scholar 

  66. H Chapel A Puel H von Bernuth C Picard JL Casanova (2005) ArticleTitleShigella sonnei meningitis due to interleukin-1 receptor-associated kinase-4 deficiency: first association with a primary immune deficiency Clin Infect Dis 40 1227–31 Occurrence Handle15825022 Occurrence Handle1:CAS:528:DC%2BD2MXktlWqu7k%3D Occurrence Handle10.1086/428733

    Article  PubMed  CAS  Google Scholar 

  67. A Enders U Pannicke R Berner P Henneke K Radlinger K Schwarz et al. (2004) ArticleTitleTwo siblings with lethal pneumococcal meningitis in a family with a mutation in interleukin-1 receptor-associated kinase 4 J Pediatr 145 698–700 Occurrence Handle15520784 Occurrence Handle10.1016/j.jpeds.2004.06.065

    Article  PubMed  Google Scholar 

  68. AJ Currie DJ Davidson GS Reid S Bharya KL MacDonald RS Devon et al. (2004) ArticleTitlePrimary immunodeficiency to pneumococcal infection due to a defect in Toll-like receptor signaling J Pediatr 144 512–8 Occurrence Handle15069402 Occurrence Handle1:CAS:528:DC%2BD2cXivVelu7g%3D Occurrence Handle10.1016/j.jpeds.2003.10.034

    Article  PubMed  CAS  Google Scholar 

  69. K Yang A Puel S Zhang C Eidenschenk CL Ku A Casrouge et al. (2005) ArticleTitleHuman TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses Immunity 23 465–78 Occurrence Handle16286015 Occurrence Handle1:CAS:528:DC%2BD2MXht12msr7J Occurrence Handle10.1016/j.immuni.2005.09.016

    Article  PubMed  CAS  Google Scholar 

  70. NC Arbour E Lorenz BC Schutte J Zabner JN Kline M Jones et al. (2000) ArticleTitleTLR4 mutations are associated with endotoxin hyporesponsiveness in humans Nat Genet 25 187–91 Occurrence Handle10835634 Occurrence Handle1:CAS:528:DC%2BD3cXjvFOgtL8%3D Occurrence Handle10.1038/76048

    Article  PubMed  CAS  Google Scholar 

  71. G Tal A Mandelberg I Dalal K Cesar E Somekh A Tal et al. (2004) ArticleTitleAssociation between common Toll-like receptor 4 mutations and severe respiratory syncytial virus disease J Infect Dis 189 2057–63 Occurrence Handle15143473 Occurrence Handle1:CAS:528:DC%2BD2cXlsFCmuro%3D Occurrence Handle10.1086/420830

    Article  PubMed  CAS  Google Scholar 

  72. A Gagro M Tominac V Krsulovic-Hresic A Bace M Matic V Drazenovic et al. (2004) ArticleTitleIncreased Toll-like receptor 4 expression in infants with respiratory syncytial virus bronchiolitis Clin Exp Immunol 135 267–72 Occurrence Handle14738455 Occurrence Handle1:CAS:528:DC%2BD2cXhvF2ltLs%3D Occurrence Handle10.1111/j.1365-2249.2004.02364.x

    Article  PubMed  CAS  Google Scholar 

  73. AC Ogus B Yoldas T Ozdemir A Uguz S Olcen I Keser et al. (2004) ArticleTitleThe Arg753GLn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease Eur Respir J 23 219–23 Occurrence Handle14979495 Occurrence Handle1:CAS:528:DC%2BD2cXitVGjtrY%3D Occurrence Handle10.1183/09031936.03.00061703

    Article  PubMed  CAS  Google Scholar 

  74. NW Schroder I Diterich A Zinke J Eckert C Draing V von Baehr et al. (2005) ArticleTitleHeterozygous Arg753Gln polymorphism of human TLR-2 impairs immune activation by Borrelia burgdorferi and protects from late stage Lyme disease J Immunol 175 2534–40 Occurrence Handle16081826

    PubMed  Google Scholar 

  75. W Eder W Klimecki L Yu E von Mutius J Riedler C Braun-Fahrlander et al. (2004) ArticleTitleToll-like receptor 2 as a major gene for asthma in children of European farmers J Allergy Clin Immunol 113 482–8 Occurrence Handle15007351 Occurrence Handle1:CAS:528:DC%2BD2cXhvFSlsbs%3D Occurrence Handle10.1016/j.jaci.2003.12.374

    Article  PubMed  CAS  Google Scholar 

  76. TR Hawn A Verbon KD Lettinga LP Zhao SS Li RJ Laws et al. (2003) ArticleTitleA common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease J Exp Med 198 1563–72 Occurrence Handle14623910 Occurrence Handle1:CAS:528:DC%2BD3sXptFOgsL0%3D Occurrence Handle10.1084/jem.20031220

    Article  PubMed  CAS  Google Scholar 

  77. SE Turvey TR Hawn (2006) ArticleTitleTowards subtlety: understanding the role of Toll-like receptor signaling in susceptibility to human infections Clin Immunol 120 IssueID1 1–9 Occurrence Handle16563867 Occurrence Handle1:CAS:528:DC%2BD28XlvF2ltb8%3D Occurrence Handle10.1016/j.clim.2006.02.003

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Infectious Genetics, The Institute of Medical Science, The University of Tokyo, 4-6-1, Shirokanedai, Minatoku, Tokyo, 108-8639, Japan

    Sachiko Akashi-Takamura & Kensuke Miyake

  2. CREST, Japan Science and Technology Corporation, Tokyo, Japan

    Sachiko Akashi-Takamura & Kensuke Miyake

Authors
  1. Sachiko Akashi-Takamura
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  2. Kensuke Miyake
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Correspondence to Kensuke Miyake.

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Akashi-Takamura, S., Miyake, K. Toll-like receptors (TLRs) and immune disorders. J Infect Chemother 12, 233–240 (2006). https://doi.org/10.1007/s10156-006-0477-4

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  • DOI: https://doi.org/10.1007/s10156-006-0477-4

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