Mechanisms of innate immune responses mediated by Toll-like receptors

Clinical and Applied Immunology Reviews

Volumn 5, Issue 3, 2005, Pages 167-183

  Yamamoto, Masahiro ^a   Akira, Shizuo ^a,b  

^a OSAKA UNIVERSITY   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

Innate immunity; TIR domain containing adaptors; Toll like receptor

Indexed keywords

IMIDAZOQUINOLINE DERIVATIVE; IMIQUIMOD; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1 RECEPTOR; INTERLEUKIN 12; INTERLEUKIN 6; LIPOPOLYSACCHARIDE; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN P40; RESIQUIMOD; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA;

CONDYLOMA; GENE EXPRESSION; HOST RESISTANCE; HUMAN; IMMUNE RESPONSE; INFLAMMATION; INNATE IMMUNITY; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN FUNCTION; REVIEW; SEPSIS; SEPTIC SHOCK; SIGNAL TRANSDUCTION;

EID: 20444439979     PISSN: 15291049     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cair.2005.02.001     Document Type: Article

References (106)

1. C.A. Janeway Jr. Approaching the asymptote? Evolution and revolution in immunology Cold Spring Harb Symp Quant Biol 54 1989 1-13
2. C.A. Janeway Jr. The immune system evolved to discriminate infectious nonself from noninfectious self Immunol Today 13 1992 11-16
3. B. Lemaitre E. Nicolas L. Michaut J.M. Reichhart J.A. Hoffmann The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults Cell 86 1996 973-983
4. C. Hashimoto K.L. Hudson K.V. Anderson The Toll gene of Drosophila, required for dorsal-ventral embryonic polarity, appears to encode a transmembrane protein Cell 52 1988 269-279
5. R. Medzhitov P. Preston-Hurlburt C.A. Janeway Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity Nature 388 1997 394-397
6. S. Akira K. Takeda Toll-like receptor signalling Nat Rev Immunol 4 2004 499-511
7. B. Beutler Inferences, questions and possibilities in Toll-like receptor signalling Nature 430 2004 257-263
8. E.T. Rietschel T. Kirikae F.U. Schade U. Mamat G. Schmidt H. Loppnow et al. Bacterial endotoxin: Molecular relationships of structure to activity and function FASEB J 8 1994 217-225
9. S.D. Wright R.A. Ramos P.S. Tobias R.J. Ulevitch J.C. Mathison CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein Science 249 1990 1431-1433
10. A. Poltorak X. He I. Smirnova M.Y. Liu C. Van Huffel X. Du et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: Mutations in Tlr4 gene Science 282 1998 2085-2088
11. S.T. Qureshi L. Lariviere G. Leveque S. Clermont K.J. Moore P. Gros et al. Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4) J Exp Med 189 1999 615-625
12. B. Beutler Tlr4: Central component of the sole mammalian LPS sensor Curr Opin Immunol 12 2000 20-26
13. K. Hoshino O. Takeuchi T. Kawai H. Sanjo T. Ogawa Y. Takeda et al. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: Evidence for TLR4 as the Lps gene product J Immunol 162 1999 3749-3752
14. J. da Silva Correia K. Soldau U. Christen P.S. Tobias R.J. Ulevitch Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex transfer from CD14 to TLR4 and MD-2 J Biol Chem 276 2001 21129-21135
15. Y. Nagai S. Akashi M. Nagafuku M. Ogata Y. Iwakura S. Akira et al. Essential role of MD-2 in LPS responsiveness and TLR4 distribution Nat Immunol 3 2002 667-672
16. R. Dziarski Relationships between adjuvant, immunosuppressive, and mitogenic activities of staphylococcal peptidoglycan Infect Immun 26 1979 508-514
17. A. Yoshimura E. Lien R.R. Ingalls E. Tuomanen R. Dziarski D. Golenbock Cutting edge: Recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2 J Immunol 163 1999 1-5
18. O. Takeuchi K. Hoshino T. Kawai H. Sanjo H. Takada T. Ogawa et al. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components Immunity 11 1999 443-451
19. D.M. Underhill A. Ozinsky A.M. Hajjar A. Stevens C.B. Wilson M. Bassetti et al. The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens Nature 401 1999 811-815
20. O. Takeuchi T. Kawai P.F. Muhlradt M. Morr J.D. Radolf A. Zychlinsky et al. Discrimination of bacterial lipoproteins by Toll-like receptor 6 Int Immunol 13 2001 933-940
21. O. Takeuchi S. Sato T. Horiuchi K. Hoshino K. Takeda Z. Dong et al. Cutting edge: Role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins J Immunol 169 2002 10-14
22. L. Alexopoulou V. Thomas M. Schnare Y. Lobet J. Anguita R.T. Schoen et al. Hyporesponsiveness to vaccination with Borrelia burgdorferi OspA in humans and in TLR1- and TLR2-deficient mice Nat Med 8 2002 878-884
23. T. Tokunaga T. Yamamoto S. Yamamoto How BCG led to the discovery of immunostimulatory DNA Jpn J Infect Dis 52 1999 1-11
24. H. Wagner Interactions between bacterial CpG-DNA and TLR9 bridge innate and adaptive immunity Curr Opin Microbiol 5 2002 62-69
25. A.M. Krieg CpG motifs in bacterial DNA and their immune effects Annu Rev Immunol 20 2002 709-760
26. H. Hemmi O. Takeuchi T. Kawai T. Kaisho S. Sato H. Sanjo et al. A Toll-like receptor recognizes bacterial DNA Nature 408 2000 740-745
27. S. Bauer C.J. Kirschning H. Hacker V. Redecke S. Hausmann S. Akira et al. Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition Proc Natl Acad Sci U S A 98 2001 9237-9242
28. F. Hayashi K.D. Smith A. Ozinsky T.R. Hawn E.C. Yi D.R. Goodlett et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 Nature 410 2001 1099-1103
29. T.L. Wyant M.K. Tanner M.B. Sztein Salmonella typhi flagella are potent inducers of proinflammatory cytokine secretion by human monocytes Infect Immun 67 1999 3619-3624
30. B.L. Jacobs J.O. Langland When two strands are better than one: The mediators and modulators of the cellular responses to double-stranded RNA Virology 219 1996 339-349
31. S. Landolfo M. Gariglio G. Gribaudo G. Garotta Double-stranded RNAs as gene activators Prog Mol Subcell Biol 14 1994 15-27
32. W.M. Chu D. Ostertag Z.W. Li L. Chang Y. Chen Y. Hu et al. JNK2 and IKKβ are required for activating the innate response to viral infection Immunity 11 1999 721-731
33. L.B. Maggi Jr. M.R. Heitmeier D. Scheuner R.J. Kaufman R.M. Buller J.A. Corbett Potential role of PKR in double-stranded RNA-induced macrophage activation EMBO J 19 2000 3630-3638
34. L. Alexopoulou A.C. Holt R. Medzhitov R.A. Flavell Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3 Nature 413 2001 732-738
35. M. Matsumoto S. Kikkawa M. Kohase K. Miyake T. Seya Establishment of a monoclonal antibody against human Toll-like receptor 3 that blocks double-stranded RNA-mediated signaling Biochem Biophys Res Commun 293 2002 1364-1369
36. R.L. Miller J.F. Gerster M.L. Owens H.B. Slade M.A. Tomai Imiquimod applied topically: A novel immune response modifier and new class of drug Int J Immunopharmacol 21 1999 1-14
37. S. Tyring Immune response modification: Imiquimod Australas J Dermatol 39 1998 S11-S13
38. H. Hemmi T. Kaisho O. Takeuchi S. Sato H. Sanjo K. Hoshino et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway Nat Immunol 3 2002 196-200
39. S.S. Diebold T. Kaisho H. Hemmi S. Akira C. Reis e Sousa Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA Science 303 2004 1529-1531
40. F. Heil H. Hemmi H. Hochrein F. Ampenberger C. Kirschning S. Akira et al. Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8 Science 303 2004 1526-1529
41. D. Zhang G. Zhang M.S. Hayden M.B. Greenblatt C. Bussey R.A. Flavell et al. A toll-like receptor that prevents infection by uropathogenic bacteria Science 303 2004 1522-1526
42. S. Akira K. Takeda T. Kaisho Toll-like receptors: Critical proteins linking innate and acquired immunity Nat Immunol 2 2001 675-680
43. M. Muzio J. Ni P. Feng V.M. Dixit IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling Science 278 1997 1612-1615
44. R. Medzhitov P. Preston-Hurlburt E. Kopp A. Stadlen C. Chen S. Ghosh C.A. Janeway Jr. MyD88 is an adaptor protein in the hToll/IL-1 receptor family signaling pathways Mol Cell 2 1998 253-258
45. S. Janssens R. Beyaert Functional diversity and regulation of different interleukin-1 receptor-associated kinase (IRAK) family members Mol Cell 11 2003 293-302
46. N. Suzuki S. Suzuki W.C. Yeh IRAK-4 as the central TIR signaling mediator in innate immunity Trends Immunol 23 2002 503-506
47. O. Adachi T. Kawai K. Takeda M. Matsumoto H. Tsutsui M. Sakagami et al. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function Immunity 9 1998 143-150
48. N. Suzuki S. Suzuki G.S. Duncan D.G. Millar T. Wada C. Mirtsos et al. Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4 Nature 416 2002 750-756
49. P. Kanakaraj P.H. Schafer D.E. Cavender Y. Wu K. Ngo P.F. Grealish et al. Interleukin (IL)-1 receptor-associated kinase (IRAK) requirement for optimal induction of multiple IL-1 signaling pathways and IL-6 production J Exp Med 187 1998 2073-2079
50. J.A. Thomas J.L. Allen M. Tsen T. Dubnicoff J. Danao X.C. Liao et al. Impaired cytokine signaling in mice lacking the IL-1 receptor-associated kinase J Immunol 163 1999 978-984
51. J.L. Swantek M.F. Tsen M.H. Cobb J.A. Thomas IL-1 receptor-associated kinase modulates host responsiveness to endotoxin J Immunol 164 2000 4301-4306
52. O. Takeuchi A. Kaufmann K. Grote T. Kawai K. Hoshino M. Morr et al. Cutting edge: Preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a toll-like receptor 2- and MyD88-dependent signaling pathway J Immunol 164 2000 554-557
53. H. Hacker R.M. Vabulas O. Takeuchi K. Hoshino S. Akira H. Wagner Immune cell activation by bacterial CpG-DNA through myeloid differentiation marker 88 and tumor necrosis factor receptor-associated factor (TRAF)6 J Exp Med 192 2000 595-600
54. M. Schnare A.C. Holt K. Takeda S. Akira R. Medzhitov Recognition of CpG DNA is mediated by signaling pathways dependent on the adaptor protein MyD88 Curr Biol 10 2000 1139-1142
55. T. Kawai O. Adachi T. Ogawa K. Takeda S. Akira Unresponsiveness of MyD88-deficient mice to endotoxin Immunity 11 1999 115-122
56. T. Kawai O. Takeuchi T. Fujita J. Inoue P.F. Muhlradt S. Sato et al. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes J Immunol 167 2001 5887-5894
57. S. Doyle S. Vaidya R. O'Connell H. Dadgostar P. Dempsey T. Wu et al. IRF3 mediates a TLR3/TLR4-specific antiviral gene program Immunity 17 2002 251-263
58. T. Horng G.M. Barton R. Medzhitov TIRAP: An adapter molecule in the Toll signaling pathway Nat Immunol 2 2001 835-841
59. K.A. Fitzgerald E.M. Palsson-McDermott A.G. Bowie C.A. Jefferies A.S. Mansell G. Brady et al. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction Nature 413 2001 78-83
60. T. Kaisho O. Takeuchi T. Kawai K. Hoshino S. Akira Endotoxin-induced maturation of MyD88-deficient dendritic cells J Immunol 166 2001 5688-5694
61. M. Yamamoto S. Sato H. Hemmi H. Sanjo S. Uematsu T. Kaisho et al. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4 Nature 420 2002 324-329
62. T. Horng G.M. Barton R.A. Flavell R. Medzhitov The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors Nature 420 2002 329-333
63. M. Yamamoto S. Sato K. Mori K. Hoshino O. Takeuchi K. Takeda et al. Cutting edge: A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-β promoter in the Toll-like receptor signaling J Immunol 169 2002 6668-6672
64. H. Oshiumi M. Matsumoto K. Funami T. Akazawa T. Seya TICAM-1, an adaptor molecule that participates in Toll-like receptor 3-mediated interferon-β induction Nat Immunol 4 2003 161-167
65. M. Yamamoto S. Sato H. Hemmi K. Hoshino T. Kaisho H. Sanjo et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway Science 301 2003 640-643
66. K. Hoebe X. Du P. Georgel E. Janssen K. Tabeta S.O. Kim et al. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling Nature 424 2003 743-748
67. L.A. O'Neill K.A. Fitzgerald A.G. Bowie The Toll-IL-1 receptor adaptor family grows to five members Trends Immunol 24 2003 286-290
68. M. Mink B. Fogelgren K. Olszewski P. Maroy K. Csiszar A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans Genomics 74 2001 234-244
69. M. Yamamoto S. Sato H. Hemmi S. Uematsu K. Hoshino T. Kaisho et al. TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway Nat Immunol 4 2003 1144-1150
70. K.A. Fitzgerald D.C. Rowe B.J. Barnes D.R. Caffrey A. Visintin E. Latz et al. LPS-TLR4 signaling to IRF-3/7 and NF-κB involves the toll adapters TRAM and TRIF J Exp Med 198 2003 1043-1055
71. H. Oshiumi M. Sasai K. Shida T. Fujita M. Matsumoto T. Seya TIR-containing adapter molecule (TICAM)-2, a bridging adapter recruiting to toll-like receptor 4 TICAM-1 that induces interferon-β J Biol Chem 278 2003 49751-49762
72. N.T. Liberati K.A. Fitzgerald D.H. Kim R. Feinbaum D.T. Golenbock F.M. Ausubel Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response Proc Natl Acad Sci U S A 101 2004 6593-6598
73. C. Couillault N. Pujol J. Reboul L. Sabatier J.F. Guichou Y. Kohara et al. TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM Nat Immunol 5 2004 488-494
74. J. Grosshans F. Schnorrer C. Nusslein-Volhard Oligomerisation of Tube and Pelle leads to nuclear localisation of dorsal Mech Dev 81 1999 127-138
75. Z. Jiang H.J. Johnson H. Nie J. Qin T.A. Bird X. Li Pellino 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 2003 10952-10956
76. K.Y. Yu H.J. Kwon D.A. Norman E. Vig M.G. Goebl M.A. Harrington Cutting edge: Mouse pellino-2 modulates IL-1 and lipopolysaccharide signaling J Immunol 169 2002 4075-4078
77. L.E. Jensen A.S. Whitehead Pellino2 activates the mitogen activated protein kinase pathway FEBS Lett 545 2003 199-202
78. L.E. Jensen A.S. Whitehead Pellino3, a novel member of the Pellino protein family, promotes activation of c-Jun and Elk-1 and may act as a scaffolding protein J Immunol 171 2003 1500-1506
79. K. Kobayashi L.D. Hernandez J.E. Galan C.A. Janeway Jr. R. Medzhitov R.A. Flavell IRAK-M is a negative regulator of Toll-like receptor signaling Cell 110 2002 191-202
80. D. Wald J. Qin Z. Zhao Y. Qian M. Naramura L. Tian et al. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling Nat Immunol 4 2003 920-927
81. C. Garlanda F. Riva N. Polentarutti C. Buracchi M. Sironi M. De Bortoli et al. Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family Proc Natl Acad Sci U S A 101 2004 3522-3526
82. E.K. Brint D. Xu H. Liu A. Dunne A.N. McKenzie L.A. O'Neill et al. ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance Nat Immunol 5 2004 373-379
83. K.A. Fitzgerald S.M. McWhirter K.L. Faia D.C. Rowe E. Latz D.T. Golenbock et al. IKKε and TBK1 are essential components of the IRF3 signaling pathway Nat Immunol 4 2003 491-496
84. S.M. McWhirter K.A. Fitzgerald J. Rosains D.C. Rowe D.T. Golenbock T. Maniatis IFN-regulatory factor 3-dependent gene expression is defective in Tbk1-deficient mouse embryonic fibroblasts Proc Natl Acad Sci U S A 101 2004 233-238
85. H. Hemmi O. Takeuchi S. Sato M. Yamamoto T. Kaisho H. Sanjo et al. The roles of two IκB kinase-related kinases in lipopolysaccharide and double stranded RNA signaling and viral infection J Exp Med 199 2004 1641-1650
86. A.K. Perry E.K. Chow J.B. Goodnough W.C. Yeh G. Cheng Differential requirement for TANK-binding kinase-1 in type I interferon responses to Toll-like receptor activation and viral infection J Exp Med 199 2004 1651-1658
87. S. Sato M. Sugiyama M. Yamamoto Y. Watanabe T. Kawai K. Takeda et al. Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-κB and IFN-regulatory factor-3, in the Toll-like receptor signaling J Immunol 171 2003 4304-4310
88. Z. Jiang T.W. Mak G. Sen X. Li Toll-like receptor 3-mediated activation of NF-κB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter inducing IFN-β Proc Natl Acad Sci U S A 101 2004 3533-3538
89. J. Gohda T. Matsumura J. Inoue Cutting edge: TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF)-dependent pathway in TLR signaling J Immunol 173 2004 2913-2917
90. E. Meylan K. Burns K. Hofmann V. Blancheteau F. Martinon M. Kelliher et al. RIP1 is an essential mediator of Toll-like receptor 3-induced NF-κB activation Nat Immunol 5 2004 503-507
91. K.J. Han X. Su L.G. Xu L.H. Bin J. Zhang H.B. Shu Mechanisms of the TRIF-induced interferon-stimulated response element and NF-κB activation and apoptosis pathways J Biol Chem 279 2004 15652-15661
92. L.C. Hsu J.M. Park K. Zhang J.L. Luo S. Maeda R.J. Kaufman et al. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4 Nature 428 2004 341-345
93. T. Kawai S. Sato K.J. Ishii C. Coban H. Hemmi M. Yamamoto et al. Interferon-α induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6 Nat Immunol 5 2004 1061-1068
94. K. Honda H. Yanai T. Mizutani H. Negishi N. Shimada N. Suzuki et al. Role of a transductional-transcriptional processor complex involving MyD88 and IRF-7 in Toll-like receptor signaling Proc Natl Acad Sci U S A 101 2004 15416-15421
95. T. Kaisho S. Akira Regulation of dendritic cell function through Toll-like receptors Curr Mol Med 3 2003 373-385
96. M. Sato H. Suemori N. Hata M. Asagiri K. Ogasawara K. Nakao et al. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-α/β gene induction Immunity 13 2000 539-548
97. S. Yamazaki T. Muta K. Takeshige A novel IκB protein, IκB-ζ, induced by proinflammatory stimuli, negatively regulates nuclear factor-kappaB in the nuclei J Biol Chem 276 2001 27657-27662
98. H. Kitamura K. Kanehira K. Okita M. Morimatsu M. Saito MAIL, a novel nuclear IκB protein that potentiates LPS-induced IL-6 production FEBS Lett 485 2000 53-56
99. H. Haruta A. Kato K. Todokoro Isolation of a novel interleukin-1-inducible nuclear protein bearing ankyrin-repeat motifs J Biol Chem 276 2001 12485-12488
100. M. Yamamoto S. Yamazaki S. Uematsu S. Sato H. Hemmi K. Hoshino et al. Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IκBζ Nature 430 2004 218-222
101. T. Shiina A. Konno T. Oonuma H. Kitamura K. Imaoka N. Takeda et al. Targeted disruption of MAIL, a nuclear IκB protein, leads to severe atopic dermatitis-like disease J Biol Chem 279 2004 55493-55498
102. P. Cristofaro S.M. Opal The Toll-like receptors and their role in septic shock Expert Opin Ther Targets 7 2003 603-612
103. S. Sakaguchi H. Negishi M. Asagiri C. Nakajima T. Mizutani A. Takaoka et al. Essential role of IRF-3 in lipopolysaccharide-induced interferon-beta gene expression and endotoxin shock Biochem Biophys Res Commun 306 2003 860-866
104. M. Karaghiosoff R. Steinborn P. Kovarik G. Kriegshauser M. Baccarini B. Donabauer et al. Central role for type I interferons and Tyk2 in lipopolysaccharide-induced endotoxin shock Nat Immunol 4 2003 471-477
105. K. Kamezaki K. Shimoda A. Numata T. Matsuda K. Nakayama M. Harada The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals Int Immunol 16 2004 1173-1179
106. M. Yamamoto K. Takeda S. Akira TIR domain-containing adaptors define the specificity of TLR signaling Mol Immunol 40 2004 861-868