Toll-like receptor cascades (Homo sapiens)

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1. Husebye H, Halaas Ø, Stenmark H, Tunheim G, Sandanger Ø, Bogen B, Brech A, Latz E, Espevik T.; ''Endocytic pathways regulate Toll-like receptor 4 signaling and link innate and adaptive immunity.''; PubMed Europe PMC Scholia
2. Piccinini AM, Midwood KS.; ''DAMPening inflammation by modulating TLR signalling.''; PubMed Europe PMC Scholia
3. Carpenter S, O'Neill LA.; ''Recent insights into the structure of Toll-like receptors and post-translational modifications of their associated signalling proteins.''; PubMed Europe PMC Scholia
4. Bas S, Neff L, Vuillet M, Spenato U, Seya T, Matsumoto M, Gabay C.; ''The proinflammatory cytokine response to Chlamydia trachomatis elementary bodies in human macrophages is partly mediated by a lipoprotein, the macrophage infectivity potentiator, through TLR2/TLR1/TLR6 and CD14.''; PubMed Europe PMC Scholia
5. Kagan JC, Su T, Horng T, Chow A, Akira S, Medzhitov R.; ''TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta.''; PubMed Europe PMC Scholia
6. Aliprantis AO, Yang RB, Mark MR, Suggett S, Devaux B, Radolf JD, Klimpel GR, Godowski P, Zychlinsky A.; ''Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor-2.''; PubMed Europe PMC Scholia
7. Wright SD, Levin SM, Jong MT, Chad Z, Kabbash LG.; ''CR3 (CD11b/CD18) expresses one binding site for Arg-Gly-Asp-containing peptides and a second site for bacterial lipopolysaccharide.''; PubMed Europe PMC Scholia
8. Erridge C.; ''Endogenous ligands of TLR2 and TLR4: agonists or assistants?''; PubMed Europe PMC Scholia
9. Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, Takeda K, Akira S.; ''Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components.''; PubMed Europe PMC Scholia
10. Akira S.; ''Toll-like receptor signaling.''; PubMed Europe PMC Scholia
11. Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO.; ''Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran.''; PubMed Europe PMC Scholia
12. Triantafilou M, Gamper FG, Haston RM, Mouratis MA, Morath S, Hartung T, Triantafilou K.; ''Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 heterodimers at the cell surface determines heterotypic associations with CD36 and intracellular targeting.''; PubMed Europe PMC Scholia
13. Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ.; ''Peptidoglycan- and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2.''; PubMed Europe PMC Scholia
14. Takeda K, Akira S.; ''TLR signaling pathways.''; PubMed Europe PMC Scholia
15. Chockalingam A, Brooks JC, Cameron JL, Blum LK, Leifer CA.; ''TLR9 traffics through the Golgi complex to localize to endolysosomes and respond to CpG DNA.''; PubMed Europe PMC Scholia
16. McNamara N, Gallup M, Sucher A, Maltseva I, McKemy D, Basbaum C.; ''AsialoGM1 and TLR5 cooperate in flagellin-induced nucleotide signaling to activate Erk1/2.''; PubMed Europe PMC Scholia
17. de Bouteiller O, Merck E, Hasan UA, Hubac S, Benguigui B, Trinchieri G, Bates EE, Caux C.; ''Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH.''; PubMed Europe PMC Scholia
18. Liu L, Botos I, Wang Y, Leonard JN, Shiloach J, Segal DM, Davies DR.; ''Structural basis of toll-like receptor 3 signaling with double-stranded RNA.''; PubMed Europe PMC Scholia
19. Gibbard RJ, Morley PJ, Gay NJ.; ''Conserved features in the extracellular domain of human toll-like receptor 8 are essential for pH-dependent signaling.''; PubMed Europe PMC Scholia
20. da Silva Correia J, Ulevitch RJ.; ''MD-2 and TLR4 N-linked glycosylations are important for a functional lipopolysaccharide receptor.''; PubMed Europe PMC Scholia
21. Takeda K, Akira S.; ''Toll-like receptors in innate immunity.''; PubMed Europe PMC Scholia
22. Hanten JA, Vasilakos JP, Riter CL, Neys L, Lipson KE, Alkan SS, Birmachu W.; ''Comparison of human B cell activation by TLR7 and TLR9 agonists.''; PubMed Europe PMC Scholia
23. Latz E, Verma A, Visintin A, Gong M, Sirois CM, Klein DC, Monks BG, McKnight CJ, Lamphier MS, Duprex WP, Espevik T, Golenbock DT.; ''Ligand-induced conformational changes allosterically activate Toll-like receptor 9.''; PubMed Europe PMC Scholia
24. Vercammen E, Staal J, Beyaert R.; ''Sensing of viral infection and activation of innate immunity by toll-like receptor 3.''; PubMed Europe PMC Scholia
25. Yamamoto M, Sato S, Mori K, Hoshino K, Takeuchi O, Takeda K, Akira S.; ''Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling.''; PubMed Europe PMC Scholia
26. Hajjar AM, O'Mahony DS, Ozinsky A, Underhill DM, Aderem A, Klebanoff SJ, Wilson CB.; ''Cutting edge: functional interactions between toll-like receptor (TLR) 2 and TLR1 or TLR6 in response to phenol-soluble modulin.''; PubMed Europe PMC Scholia
27. Wright SD, Jong MT.; ''Adhesion-promoting receptors on human macrophages recognize Escherichia coli by binding to lipopolysaccharide.''; PubMed Europe PMC Scholia
28. Núñez Miguel R, Wong J, Westoll JF, Brooks HJ, O'Neill LA, Gay NJ, Bryant CE, Monie TP.; ''A dimer of the Toll-like receptor 4 cytoplasmic domain provides a specific scaffold for the recruitment of signalling adaptor proteins.''; PubMed Europe PMC Scholia
29. Wagner H.; ''The immunobiology of the TLR9 subfamily.''; PubMed Europe PMC Scholia
30. Häcker H, Mischak H, Miethke T, Liptay S, Schmid R, Sparwasser T, Heeg K, Lipford GB, Wagner H.; ''CpG-DNA-specific activation of antigen-presenting cells requires stress kinase activity and is preceded by non-specific endocytosis and endosomal maturation.''; PubMed Europe PMC Scholia
31. Yu L, Wang L, Chen S.; ''Endogenous toll-like receptor ligands and their biological significance.''; PubMed Europe PMC Scholia
32. Aki D, Minoda Y, Yoshida H, Watanabe S, Yoshida R, Takaesu G, Chinen T, Inaba T, Hikida M, Kurosaki T, Saeki K, Yoshimura A.; ''Peptidoglycan and lipopolysaccharide activate PLCgamma2, leading to enhanced cytokine production in macrophages and dendritic cells.''; PubMed Europe PMC Scholia
33. Fitzgerald KA, Rowe DC, Golenbock DT.; ''Endotoxin recognition and signal transduction by the TLR4/MD2-complex.''; PubMed Europe PMC Scholia
34. Akashi S, Saitoh S, Wakabayashi Y, Kikuchi T, Takamura N, Nagai Y, Kusumoto Y, Fukase K, Kusumoto S, Adachi Y, Kosugi A, Miyake K.; ''Lipopolysaccharide interaction with cell surface Toll-like receptor 4-MD-2: higher affinity than that with MD-2 or CD14.''; PubMed Europe PMC Scholia
35. Ewald SE, Engel A, Lee J, Wang M, Bogyo M, Barton GM.; ''Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase.''; PubMed Europe PMC Scholia
36. Troelstra A, de Graaf-Miltenburg LA, van Bommel T, Verhoef J, Van Kessel KP, Van Strijp JA.; ''Lipopolysaccharide-coated erythrocytes activate human neutrophils via CD14 while subsequent binding is through CD11b/CD18.''; PubMed Europe PMC Scholia
37. Means TK, Wang S, Lien E, Yoshimura A, Golenbock DT, Fenton MJ.; ''Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis.''; PubMed Europe PMC Scholia
38. Funami K, Matsumoto M, Oshiumi H, Akazawa T, Yamamoto A, Seya T.; ''The cytoplasmic 'linker region' in Toll-like receptor 3 controls receptor localization and signaling.''; PubMed Europe PMC Scholia
39. Gangloff M, Gay NJ.; ''MD-2: the Toll 'gatekeeper' in endotoxin signalling.''; PubMed Europe PMC Scholia
40. Sen GC, Sarkar SN.; ''Transcriptional signaling by double-stranded RNA: role of TLR3.''; PubMed Europe PMC Scholia
41. Hoarau C, Gérard B, Lescanne E, Henry D, François S, Lacapère JJ, El Benna J, Dang PM, Grandchamp B, Lebranchu Y, Gougerot-Pocidalo MA, Elbim C.; ''TLR9 activation induces normal neutrophil responses in a child with IRAK-4 deficiency: involvement of the direct PI3K pathway.''; PubMed Europe PMC Scholia
42. McGettrick AF, Brint EK, Palsson-McDermott EM, Rowe DC, Golenbock DT, Gay NJ, Fitzgerald KA, O'Neill LA.; ''Trif-related adapter molecule is phosphorylated by PKC{epsilon} during Toll-like receptor 4 signaling.''; PubMed Europe PMC Scholia
43. Barton GM, Kagan JC, Medzhitov R.; ''Intracellular localization of Toll-like receptor 9 prevents recognition of self DNA but facilitates access to viral DNA.''; PubMed Europe PMC Scholia
44. Okusawa T, Fujita M, Nakamura J, Into T, Yasuda M, Yoshimura A, Hara Y, Hasebe A, Golenbock DT, Morita M, Kuroki Y, Ogawa T, Shibata K.; ''Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by toll-like receptors 2 and 6.''; PubMed Europe PMC Scholia
45. Chen J, Nag S, Vidi PA, Irudayaraj J.; ''Single molecule in vivo analysis of toll-like receptor 9 and CpG DNA interaction.''; PubMed Europe PMC Scholia
46. da Silva Correia J, Soldau K, Christen U, Tobias PS, Ulevitch RJ.; ''Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. transfer from CD14 to TLR4 and MD-2.''; PubMed Europe PMC Scholia
47. Cot M, Ray A, Gilleron M, Vercellone A, Larrouy-Maumus G, Armau E, Gauthier S, Tiraby G, Puzo G, Nigou J.; ''Lipoteichoic acid in Streptomyces hygroscopicus: structural model and immunomodulatory activities.''; PubMed Europe PMC Scholia
48. Huai W, Song H, Wang L, Li B, Zhao J, Han L, Gao C, Jiang G, Zhang L, Zhao W.; ''Phosphatase PTPN4 preferentially inhibits TRIF-dependent TLR4 pathway by dephosphorylating TRAM.''; PubMed Europe PMC Scholia
49. Nyman T, Stenmark P, Flodin S, Johansson I, Hammarström M, Nordlund P.; ''The crystal structure of the human toll-like receptor 10 cytoplasmic domain reveals a putative signaling dimer.''; PubMed Europe PMC Scholia
50. Massari P, Visintin A, Gunawardana J, Halmen KA, King CA, Golenbock DT, Wetzler LM.; ''Meningococcal porin PorB binds to TLR2 and requires TLR1 for signaling.''; PubMed Europe PMC Scholia
51. Hasan U, Chaffois C, Gaillard C, Saulnier V, Merck E, Tancredi S, Guiet C, Brière F, Vlach J, Lebecque S, Trinchieri G, Bates EE.; ''Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88.''; PubMed Europe PMC Scholia
52. Zhang Z, Louboutin JP, Weiner DJ, Goldberg JB, Wilson JM.; ''Human airway epithelial cells sense Pseudomonas aeruginosa infection via recognition of flagellin by Toll-like receptor 5.''; PubMed Europe PMC Scholia
53. Smith MF, Mitchell A, Li G, Ding S, Fitzmaurice AM, Ryan K, Crowe S, Goldberg JB.; ''Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells.''; PubMed Europe PMC Scholia
54. Tao N, Wagner SJ, Lublin DM.; ''CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails.''; PubMed Europe PMC Scholia
55. Divanovic S, Trompette A, Atabani SF, Madan R, Golenbock DT, Visintin A, Finberg RW, Tarakhovsky A, Vogel SN, Belkaid Y, Kurt-Jones EA, Karp CL.; ''Negative regulation of Toll-like receptor 4 signaling by the Toll-like receptor homolog RP105.''; PubMed Europe PMC Scholia
56. Tanimura N, Saitoh S, Matsumoto F, Akashi-Takamura S, Miyake K.; ''Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling.''; PubMed Europe PMC Scholia
57. Takeshita F, Gursel I, Ishii KJ, Suzuki K, Gursel M, Klinman DM.; ''Signal transduction pathways mediated by the interaction of CpG DNA with Toll-like receptor 9.''; PubMed Europe PMC Scholia
58. Chockalingam A, Cameron JL, Brooks JC, Leifer CA.; ''Negative regulation of signaling by a soluble form of toll-like receptor 9.''; PubMed Europe PMC Scholia
59. Fenton MJ, Golenbock DT.; ''LPS-binding proteins and receptors.''; PubMed Europe PMC Scholia
60. Heine H, Ulmer AJ.; ''Recognition of bacterial products by toll-like receptors.''; PubMed Europe PMC Scholia
61. Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S.; ''Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8.''; PubMed Europe PMC Scholia
62. Latz E, Schoenemeyer A, Visintin A, Fitzgerald KA, Monks BG, Knetter CF, Lien E, Nilsen NJ, Espevik T, Golenbock DT.; ''TLR9 signals after translocating from the ER to CpG DNA in the lysosome.''; PubMed Europe PMC Scholia
63. Wei T, Gong J, Jamitzky F, Heckl WM, Stark RW, Rössle SC.; ''Homology modeling of human Toll-like receptors TLR7, 8, and 9 ligand-binding domains.''; PubMed Europe PMC Scholia
64. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, Horiuchi T, Tomizawa H, Takeda K, Akira S.; ''Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway.''; PubMed Europe PMC Scholia
65. Beutler B.; ''Inferences, questions and possibilities in Toll-like receptor signalling.''; PubMed Europe PMC Scholia
66. Ohnishi T, Muroi M, Tanamoto K.; ''N-linked glycosylations at Asn(26) and Asn(114) of human MD-2 are required for toll-like receptor 4-mediated activation of NF-kappaB by lipopolysaccharide.''; PubMed Europe PMC Scholia
67. Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, Takeuchi O, Takeda K, Akira S.; ''TRAM is specifically involved in the Toll-like receptor 4-mediated MyD88-independent signaling pathway.''; PubMed Europe PMC Scholia
68. Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A.; ''The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5.''; PubMed Europe PMC Scholia
69. Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO.; ''The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex.''; PubMed Europe PMC Scholia
70. Manukyan M, Triantafilou K, Triantafilou M, Mackie A, Nilsen N, Espevik T, Wiesmüller KH, Ulmer AJ, Heine H.; ''Binding of lipopeptide to CD14 induces physical proximity of CD14, TLR2 and TLR1.''; PubMed Europe PMC Scholia
71. Wright SD, Tobias PS, Ulevitch RJ, Ramos RA.; ''Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages.''; PubMed Europe PMC Scholia
72. Kawai T, Akira S.; ''TLR signaling.''; PubMed Europe PMC Scholia
73. Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO.; ''Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide.''; PubMed Europe PMC Scholia
74. Tokisue T, Watanabe T, Tsujita T, Nishikawa S, Hasegawa T, Seya T, Matsumoto M, Fukuda K.; ''Significance of the N-terminal histidine-rich region for the function of the human toll-like receptor 3 ectodomain.''; PubMed Europe PMC Scholia
75. Kishore U, Greenhough TJ, Waters P, Shrive AK, Ghai R, Kamran MF, Bernal AL, Reid KB, Madan T, Chakraborty T.; ''Surfactant proteins SP-A and SP-D: structure, function and receptors.''; PubMed Europe PMC Scholia
76. Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H, Lipford G, Bauer S.; ''Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848.''; PubMed Europe PMC Scholia
77. Cherfils-Vicini J, Platonova S, Gillard M, Laurans L, Validire P, Caliandro R, Magdeleinat P, Mami-Chouaib F, Dieu-Nosjean MC, Fridman WH, Damotte D, Sautès-Fridman C, Cremer I.; ''Triggering of TLR7 and TLR8 expressed by human lung cancer cells induces cell survival and chemoresistance.''; PubMed Europe PMC Scholia
78. Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa C.; ''Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.''; PubMed Europe PMC Scholia
79. Govindaraj RG, Manavalan B, Basith S, Choi S.; ''Comparative analysis of species-specific ligand recognition in Toll-like receptor 8 signaling: a hypothesis.''; PubMed Europe PMC Scholia
80. Takeuchi O, Kawai T, Mühlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S.; ''Discrimination of bacterial lipoproteins by Toll-like receptor 6.''; PubMed Europe PMC Scholia
81. Kagan JC, Medzhitov R.; ''Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling.''; PubMed Europe PMC Scholia
82. Kawai T, Akira S.; ''Pathogen recognition with Toll-like receptors.''; PubMed Europe PMC Scholia
83. Schaefer L.; ''Complexity of danger: the diverse nature of damage-associated molecular patterns.''; PubMed Europe PMC Scholia
84. Li Y, Chen M, Cao H, Zhu Y, Zheng J, Zhou H.; ''Extraordinary GU-rich single-strand RNA identified from SARS coronavirus contributes an excessive innate immune response.''; PubMed Europe PMC Scholia
85. Ewald SE, Lee BL, Lau L, Wickliffe KE, Shi GP, Chapman HA, Barton GM.; ''The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor.''; PubMed Europe PMC Scholia
86. Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R, Barton GM, Granucci F, Kagan JC.; ''CD14 controls the LPS-induced endocytosis of Toll-like receptor 4.''; PubMed Europe PMC Scholia
87. Elner SG, Petty HR, Elner VM, Yoshida A, Bian ZM, Yang D, Kindzelskii AL.; ''TLR4 mediates human retinal pigment epithelial endotoxin binding and cytokine expression.''; PubMed Europe PMC Scholia
88. Chiang CY, Veckman V, Limmer K, David M.; ''Phospholipase Cγ-2 and intracellular calcium are required for lipopolysaccharide-induced Toll-like receptor 4 (TLR4) endocytosis and interferon regulatory factor 3 (IRF3) activation.''; PubMed Europe PMC Scholia

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External references

DataNodes

Name	Type	Database reference	Comment
2xN4GlycoAsn-LY96	Protein	Q9Y6Y9 (Uniprot-TrEMBL)
2xN4GlycoAsn-TLR4	Protein	O00206 (Uniprot-TrEMBL)
4xPalmC-CD36	Protein	P16671 (Uniprot-TrEMBL)
4xPalmC-CD36	Protein	P16671 (Uniprot-TrEMBL)
Activated TLR1:2 or TLR 2:6 heterodimers or TLR4 homodimer		R-HSA-181230 (Reactome)
C-ter TLR9 dimer:unmethylated CpG DNA	Complex	R-HSA-1679087 (Reactome)
C-ter-TLR9 dimer	Complex	R-HSA-1679581 (Reactome)
CD14(20-345)	Protein	P08571 (Uniprot-TrEMBL)
CD14(20-345)	Protein	P08571 (Uniprot-TrEMBL)
CD14		R-HSA-166029 (Reactome)
CD180	Protein	Q99467 (Uniprot-TrEMBL)
Clostridial peptidoglycan	Metabolite	CHEBI:8005 (ChEBI)
Diacyl lipopeptide	Metabolite	CHEBI:46896 (ChEBI)
Dynamin-1/2/3		R-HSA-446847 (Reactome)
EEA1	Protein	Q15075 (Uniprot-TrEMBL)
EEA1:EEA1	Complex	R-HSA-187897 (Reactome)
Flagellin	Protein	P04949 (Uniprot-TrEMBL)
Flagellin	Protein	P04949 (Uniprot-TrEMBL)
GPIN-CD14(20-345)	Protein	P08571 (Uniprot-TrEMBL)
GPIN-CD14(20-345)	Protein	P08571 (Uniprot-TrEMBL)
IMIQ	Metabolite	CHEBI:36704 (ChEBI)
ITGAM	Protein	P11215 (Uniprot-TrEMBL)
ITGB2	Protein	P05107 (Uniprot-TrEMBL)
Integrin alphaMbeta2	Complex	R-HSA-202755 (Reactome)
LBP	Protein	P18428 (Uniprot-TrEMBL)
LBP:bacterial LPS	Complex	R-HSA-166013 (Reactome)
LBP	Protein	P18428 (Uniprot-TrEMBL)
LPS	Metabolite	CHEBI:16412 (ChEBI)
LPS:CD14:CR3	Complex	R-HSA-2559438 (Reactome)
LPS:CD14		R-HSA-166043 (Reactome)
LPS:GPI-anchored CD14	Complex	R-HSA-166034 (Reactome)
LPS:secreted CD14	Complex	R-HSA-166026 (Reactome)
LPS		CHEBI:16412 (ChEBI)
LY86	Protein	O95711 (Uniprot-TrEMBL)
LY96	Protein	Q9Y6Y9 (Uniprot-TrEMBL)
Ligand recognized by TLR10		R-NUL-168948 (Reactome)
Ligands recognized by TLR7 and TLR8		R-ALL-1216505 (Reactome)
Lipoteichoic acid	Metabolite	CHEBI:28640 (ChEBI)
MAL:PI(4,5)P2:activated TLR2/4	Complex	R-HSA-2559411 (Reactome)
MAL:PI(4,5)P2	Complex	R-HSA-2559415 (Reactome)
Major outer membrane protein P	Protein	P30690 (Uniprot-TrEMBL)
MyD88 cascade initiated on plasma membrane	Pathway	R-HSA-975871 (Reactome)	Mammalian myeloid differentiation factor 88 (MyD88) is Toll/interleukin (IL)-1 (TIR)-domain containing adapter protein which plays crucial role in TLR signaling. All TLRs, with only one exception of TLR3, can initiate downstream signaling trough MyD88. In the MyD88 - dependent pathway, once the adaptor is bound to TLR it leads to recruitment of IL1 receptor associated kinase family IRAK which is followed by activation of tumour necrosis factor receptor-associated factor 6 (TRAF6) . TRAF6 is an ubiquitin E3 ligase which in turn induces TGF-beta activating kinase 1 (TAK1) auto phosphorylation. Once activated TAK1 can ultimately mediate the induction of the transcription factor NF-kB or the mitogen-activated protein kinases (MAPK), such as JNK, p38 and ERK. This results in the translocation of the activated NF-kB and MAPKs to the nucleus and the initiation of appropriate gene transcription leading to the production of many proinflammatory cytokines and antimicrobial peptides.
MyD88 dependent cascade initiated on endosome	Pathway	R-HSA-975155 (Reactome)	Upon binding of their ligands, TLR7/8 and TLR9 recruit a cytoplasmic adaptor MyD88 and IRAKs, downstream of which the signaling pathways are divided to induce either inflammatory cytokines or type I IFNs.
MyD88-independent TLR3/TLR4 cascade	Pathway	R-HSA-166166 (Reactome)	MyD88-independent signaling pathway is shared by TLR3 and TLR4 cascades. TIR-domain-containing adapter-inducing interferon-beta (TRIF or TICAM1) is a key adapter molecule in transducing signals from TLR3 and TLR4 in a MyD88-independent manner (Yamamoto M et al. 2003a). TRIF is recruited to ligand-stimulated TLR3 or 4 complex via its TIR domain. TLR3 directly binds TRIF (Oshiumi H et al 2003). In contrast, TLR4-mediated signaling pathway requires two adapter molecules, TRAM (TRIF-related adapter molecule or TICAM2) and TRIF. TRAM(TICAM2) is thought to bridge between the activated TLR4 complex and TRIF (Yamamoto M et al. 2003b, Tanimura N et al. 2008, Kagan LC et al. 2008). TRIF recruitment to TLR complex stimulates distinct pathways leading to production of type 1 interferons (IFNs), pro-inflammatory cytokines and induction of programmed cell death.
MyD88:Mal cascade initiated on plasma membrane	Pathway	R-HSA-166058 (Reactome)	The first known downstream component of TLR4 and TLR2 signaling is the adaptor MyD88. Another adapter MyD88-adaptor-like (Mal; also known as TIR-domain-containing adaptor protein or TIRAP) has also been described for TLR4 and TLR2 signaling. MyD88 comprises an N-terminal Death Domain (DD) and a C-terminal TIR, whereas Mal lacks the DD. The TIR homotypic interactions bring adapters into contact with the activated TLRs, whereas the DD modules recruit serine/threonine kinases such as interleukin-1-receptor-associated kinase (IRAK). Recruitment of these protein kinases is accompanied by phosphorylation, which in turn results in the interaction of IRAKs with TNF-receptor-associated factor 6 (TRAF6). The oligomerization of TRAF6 activates TAK1, a member of the MAP3-kinase family, and this leads to the activation of the IkB kinases. These kinases, in turn, phosphorylate IkB, leading to its proteolytic degradation and the translocation of NF-kB to the nucleus. Concomitantly, members of the activator protein-1 (AP-1) transcription factor family, Jun and Fos, are activated, and both AP-1 transcription factors and NF-kB are required for cytokine production, which in turn produces downstream inflammatory effects.
MyrG-p-S16-TICAM2	Protein	Q86XR7 (Uniprot-TrEMBL)
MyrG-p-S16-TICAM2	Protein	Q86XR7 (Uniprot-TrEMBL)
N-ter TLR9 dimer:unmethylated CpG DNA	Complex	R-HSA-1679094 (Reactome)
N-ter TLR9 dimer	Complex	R-HSA-1679574 (Reactome)
PI(4,5)P2	Metabolite	CHEBI:18348 (ChEBI)
PI(4,5)P2	Metabolite	CHEBI:18348 (ChEBI)
PI3K class III	Complex	R-HSA-188015 (Reactome)
PIK3C3	Protein	Q8NEB9 (Uniprot-TrEMBL)
PIK3R4	Protein	Q99570 (Uniprot-TrEMBL)
PLCG2	Protein	P16885 (Uniprot-TrEMBL)
Pulmonory surfactant proteins A and D		R-HSA-391108 (Reactome)
R-848	Metabolite	CHEBI:36706 (ChEBI)
RP105:MD1	Complex	R-HSA-166154 (Reactome)
TIRAP	Protein	P58753 (Uniprot-TrEMBL)
TIRAP	Protein	P58753 (Uniprot-TrEMBL)
TLR1(19-786)	Protein	Q5FWG5 (Uniprot-TrEMBL)
TLR10	Protein	Q9BXR5 (Uniprot-TrEMBL)
TLR10 homodimer bound to ligand	Complex	R-HSA-188116 (Reactome)
TLR10	Protein	Q9BXR5 (Uniprot-TrEMBL)
TLR1:TLR2 ligand:CD14	Complex	R-HSA-2559462 (Reactome)
TLR1:TLR2 recognized ligand		R-NME-168944 (Reactome)
TLR1:TLR2:TLR1/2 ligand:CD14	Complex	R-HSA-181226 (Reactome)
TLR1:TLR2	Complex	R-HSA-168946 (Reactome)
TLR2	Protein	O60603 (Uniprot-TrEMBL)
TLR3	Protein	O15455 (Uniprot-TrEMBL)
TLR3	Protein	O15455 (Uniprot-TrEMBL)
TLR4	Protein	O00206 (Uniprot-TrEMBL)
TLR4:LY96:LPS:CD14	Complex	R-HSA-166850 (Reactome)
TLR4:LY96:LPS:CD14	Complex	R-HSA-2201299 (Reactome)
TLR4:LY96	Complex	R-HSA-166050 (Reactome)
TLR5 homodimer:bacterial flagellin	Complex	R-HSA-188027 (Reactome)
TLR5	Protein	O60602 (Uniprot-TrEMBL)
TLR5	Protein	O60602 (Uniprot-TrEMBL)
TLR6	Protein	Q9Y2C9 (Uniprot-TrEMBL)
TLR6/2 ligand:CD14:CD36	Complex	R-HSA-2559461 (Reactome)
TLR6:TLR2 recognized ligand		R-ALL-181407 (Reactome)
TLR6:TLR2:ligand:CD14:CD36	Complex	R-HSA-181410 (Reactome)
TLR6:TLR2	Complex	R-HSA-168949 (Reactome)
TLR7 or TLR8:recognized ligand	Complex	R-HSA-188132 (Reactome)
TLR7 or TLR8		R-HSA-188166 (Reactome)
TLR7(?-1049)	Protein	Q9NYK1 (Uniprot-TrEMBL)
TLR8	Protein	Q9NR97 (Uniprot-TrEMBL)
TLR9	Protein	Q9NR96 (Uniprot-TrEMBL)
TLR9(1-?)	Protein	Q9NR96 (Uniprot-TrEMBL)
TLR9(?-1032)	Protein	Q9NR96 (Uniprot-TrEMBL)
TLR9	Protein	Q9NR96 (Uniprot-TrEMBL)
TRAM:TLR4:LY96:LPS:CD14	Complex	R-HSA-166163 (Reactome)
Trafficking and processing of endosomal TLR	Pathway	R-HSA-1679131 (Reactome)	Mammalian TLR3, TLR7, TLR8, TLR9 are endosomal receptors that sense nucleic acids that have been released from endocytosed/phagocytosed bacteria, viruses or parasites. These TLRs have a ligand-recognition domain that faces the lumen of the endosome (which is topologically equivalent to the outside of the cell), a transmembrane domain, and a signaling domain that faces the cytosol. Under normal conditions, self nucleic acids are not recognized by TLRs due to multiple levels of regulation including receptor compartmentalization, trafficking and proteolytic processing (Barton GM et al 2006, Ewald SE et al 2008). At steady state TLR3, TLR7, TLR8, TLR9 reside primarily in the endoplasmic reticulum (ER), however, their activation by specific ligands only occurs within acidified endolysosomal compartments (Hacker H et al 1998, Funami K et al 2004, Gibbard RJ et al 2006). Several chaperon proteins associate with TLRs in the ER to provide efficient translocation to endolysosome. Upon reaching endolysosomal compartments the ectodomains of TLR7 and TLR9 are proteolytically cleaved by cysteine endoproteases. Both full-length and cleaved C-terminus of TLR9 bind CpG-oligodeoxynucleotides, however it has been proposed that only the processed receptor is functional. Although similar cleavage of TLR3 has been reported by Ewald et al 2011, other studies demonstrated that the N-terminal region of TLR3 ectodomain was implicated in ligand binding, thus TLR3 may function as a full-length receptor (Liu L et al 2008, Tokisue T et al 2008). There are no data on TLR8 processing, although the cell biology of TLR8 is probably similar to TLR9 and TLR7 (Gibbard RJ et al 2006, Wei T et al 2009).
Triacyl lipopeptide	Metabolite	CHEBI:60192 (ChEBI)
Unmethylated CpG DNA		R-NUL-167913 (Reactome)
Viral dsRNA (-) stranded		R-NUL-434118 (Reactome)
ZFYVE20	Protein	Q9H1K0 (Uniprot-TrEMBL)
activated TLR9:PI3K class III	Complex	R-HSA-188017 (Reactome)
fl-TLR9:unmethylated CpG DNA	Complex	R-HSA-187884 (Reactome)
viral dsRNA :TLR3	Complex	R-HSA-167985 (Reactome)

Annotated Interactions

Source	Target	Type	Database reference	Comment
4xPalmC-CD36			R-HSA-2559464 (Reactome)
Activated TLR1:2 or TLR 2:6 heterodimers or TLR4 homodimer			R-HSA-2201316 (Reactome)
	C-ter TLR9 dimer:unmethylated CpG DNA	Arrow	R-HSA-187895 (Reactome)
C-ter TLR9 dimer:unmethylated CpG DNA			R-HSA-188002 (Reactome)
C-ter-TLR9 dimer			R-HSA-187895 (Reactome)
CD14(20-345)			R-HSA-169719 (Reactome)
Dynamin-1/2/3		Arrow	R-HSA-2201293 (Reactome)
EEA1:EEA1		Arrow	R-HSA-1679098 (Reactome)
EEA1:EEA1		Arrow	R-HSA-187895 (Reactome)
Flagellin			R-HSA-188025 (Reactome)
GPIN-CD14(20-345)			R-HSA-166038 (Reactome)
GPIN-CD14(20-345)			R-HSA-2559464 (Reactome)
GPIN-CD14(20-345)			R-HSA-2559468 (Reactome)
Integrin alphaMbeta2			R-HSA-2559439 (Reactome)
	LBP:bacterial LPS	Arrow	R-HSA-166015 (Reactome)
LBP:bacterial LPS			R-HSA-166038 (Reactome)
LBP:bacterial LPS			R-HSA-169719 (Reactome)
	LBP	Arrow	R-HSA-166038 (Reactome)
	LBP	Arrow	R-HSA-169719 (Reactome)
LBP			R-HSA-166015 (Reactome)
	LPS:CD14:CR3	Arrow	R-HSA-2559439 (Reactome)
LPS:CD14			R-HSA-166041 (Reactome)
LPS:CD14			R-HSA-2559439 (Reactome)
	LPS:GPI-anchored CD14	Arrow	R-HSA-166038 (Reactome)
	LPS:secreted CD14	Arrow	R-HSA-169719 (Reactome)
LPS			R-HSA-166015 (Reactome)
Ligand recognized by TLR10			R-HSA-168947 (Reactome)
Ligands recognized by TLR7 and TLR8			R-HSA-167983 (Reactome)
	MAL:PI(4,5)P2:activated TLR2/4	Arrow	R-HSA-2201316 (Reactome)
	MAL:PI(4,5)P2	Arrow	R-HSA-2559456 (Reactome)
MAL:PI(4,5)P2			R-HSA-2201316 (Reactome)
	MyrG-p-S16-TICAM2	Arrow	R-HSA-2201341 (Reactome)
MyrG-p-S16-TICAM2			R-HSA-166168 (Reactome)
MyrG-p-S16-TICAM2			R-HSA-2201341 (Reactome)
	N-ter TLR9 dimer:unmethylated CpG DNA	Arrow	R-HSA-1679098 (Reactome)
N-ter TLR9 dimer			R-HSA-1679098 (Reactome)
PI(4,5)P2			R-HSA-2559456 (Reactome)
PI3K class III			R-HSA-188002 (Reactome)
PLCG2		Arrow	R-HSA-2201293 (Reactome)
Pulmonory surfactant proteins A and D		TBar	R-HSA-166041 (Reactome)
Pulmonory surfactant proteins A and D		TBar	R-HSA-168951 (Reactome)
			R-HSA-166015 (Reactome)	Lipopolysaccharide-binding protein (LBP) is a ~60-kDa serum glycoprotein which transfers LPS to both membrane-bound and soluble CD14. The LPS binding site of LBP consists of basic residues that bind the phosphorylated head of the bacterial lipid A. LBP is an acute-phase opsonin that binds gram-negative bacteria and bacterial fragments and promote the interaction of coated bacteria with phagocytes.
			R-HSA-166038 (Reactome)	At the beginning of this reaction, 1 molecule of 'GPI-anchored form of CD14', and 1 molecule of 'LBP complexed with bacterial LPS' are present. At the end of this reaction, 1 molecule of 'LPS complexed with GPI-anchored CD14', and 1 molecule of 'LBP' are present.
			R-HSA-166041 (Reactome)	The Toll-like receptor 4 (TLR4) is a membrane-spanning protein distantly related to the IL1 receptor. Both CD14 and members of the Toll family contain multiple leucine-rich repeats. In addition, the latter possess a Toll-homology domain in the cytoplasmic tail, which is important in the generation of a transmembrane signal linked to LPS-induced cell activation. Of all Toll family members, TLR4 is probably the exclusive receptor for LPS from most Gram negative organisms. Toll-like receptor 4 and lymphocyte antigen 96 (LY96, also known as myeloid differentiation factor 2 (MD2)) form a heterodimer that specifically recognizes structurally diverse LPS molecules. A structural study of TLR4:LY96 complex revealed that LY96 (MD2) interaction with TLR4 relies on hydrogen and electrostatic bonds (Kim HM et al, 2007). LPS binds to the hydrophobic pocket of LY96 and directly mediates the dimerization of the two TLR4:LY96 complexes in a symmetrical manner. Both hydrophobic and hydrophilic interactions contribute to the main dimerization interaction between LY96, LPS and TLR4 multimer components. The phosphate groups of LPS also contribute to the receptor multimerization by forming ionic interactions with positively charged residues of TLR4 and LY96. (Park BS et al, 2009). The activated TLR4 receptor is composed of two copies of the TLR4:LY96:LPS complex and initiates signal transduction by recruiting intracellular adaptor molecules.
			R-HSA-166168 (Reactome)	TRIF-related adapter molecule (TRAM, also called TIRP or TICAM2) is 235 amino acids in length, and its TIR domain is most closely related to TRIF (and hence its name). Notably, both human and mouse TRAM contain a cysteine (C117 in humans) at the position where other adapters and TLRs have a conserved proline, although an adjacent proline (P116) is present. TRAM associates with TLR4 and TRIF, as well as the non-canonical NFkB kinases, IKK epsilon, and TBK1, which phosphorylate IRF3. TRAM provides specificity for the MyD88-independent component of TLR4 signaling.
			R-HSA-1679098 (Reactome)	TLR9 traffics to an endosomal vesicle where it is processed by cathepsin S at neural pH to generate an N-terminal product (TLR9 N-ter, aa 1-723). The N-terminal fragment of TLR9 also binds ligand, but in contrast to the C-terminal fragment it inhibits TLR9 signaling. Thus, a proper balance between the two proteolytic events probably regulates TLR9-mediated host responses. (Chockalingam A et al 2011).
			R-HSA-1679589 (Reactome)	Both the full-length receptor and cleaved fragment corresponding to the C-terminal part of TLR9 were capable to bind ligand, however only processed form (TLR9 C-ter, aa 471-1032) was shown to bind MyD88 and induce signaling in different mouse cells (Ewald SE et al 2008,).
			R-HSA-167983 (Reactome)	Endosomal recognition of influenza genomic RNA and imidazoquinoline compounds occurs by means of TLR7 and TLR8.
			R-HSA-168092 (Reactome)	Viral dsRNA triggers an antiviral pathway mediated by toll like receptor 3. TLR3 dimerization occurs upon ligand binding to positivly charged residues on the ectodomain termini of TLR3 wich are responsible for the interaction with sugar-phosphate groups of dsRNA.
			R-HSA-168947 (Reactome)	Microbal stimulation was shown to alter mRNA expression of TLR10 in human granulocytes, monocytes[Zarember KA and Godowski P 2002] and B cells[Bourke ED et al 2003]. However the natural ligand of TLR10 remains unknown.
			R-HSA-168950 (Reactome)	TLR2 - in combination with TLR6 - plays a major role in recognizing lipoteichoic acid (LTA) and peptidoglycan wall products from Gram-positive bacteria, as well as Mycobacterial diacylated lipopeptides.
			R-HSA-168951 (Reactome)	The TLR2:TLR1 complex recognizes Neisserial PorB and Mycobacterial triacylated lipoproteins and peptides, amongst others.
			R-HSA-169719 (Reactome)	At the beginning of this reaction, 1 molecule of 'Secreted form of CD14', and 1 molecule of 'LBP complexed with bacterial LPS' are present. At the end of this reaction, 1 molecule of 'LBP', and 1 molecule of 'LPS complexed with secreted CD14' are present.
			R-HSA-187895 (Reactome)	Synthetic oligodeoxynucleotides (ODN) expressing non-methylated CpG motifs patterned after those present in bacterial DNA have characteristic immunomodulatory effects. CpG DNA is recognized as a pathogen-associated molecular pattern by TLR9, and triggers a rapid innate immune response.
			R-HSA-188002 (Reactome)	TLR9 signaling has the uncommon property of triggering PI3K-mediated cascades via Rab5.
			R-HSA-188025 (Reactome)	Fragments of extracelllar flagellin bind the TLR5 homodimer.
			R-HSA-2201293 (Reactome)	Upon LPS stimulation TLR4 is internalized into endosomes where the signaling pathway is triggered through the adaptors TRAM and TRIF leading to the activation of IRF3 and induction of IFN-beta [Tanimuro N et al 2008; Kagan JC et al 2008]. While TLR4 translocation to endosomes is governed by known regulators of general endocytic processes such as dynamins and clathrin, other proteins that specifically regulate LPS-stimulated TLR4 endocytosis have been also identified [Husebye et al 2006; Kagan JC et al 2008; Zanoni I et al 2011]. Thus, CD14 has been implicated both in transporting LPS to TLR4 and in delivering TLR4 to an endosomal compartment. TLR4 translocation activated by CD14 appears to be Syk-mediated, and requires its downstream effector phospholipase C gamma 2 (PLCgamma2), which in turn induces a drop in the concentration of PIP2 required for endosomal sealing [Zanoni I et al 2011]. It has also been shown that PLCgamma2 induces inositol 1,4,5-trisphosphate (IP(3)) production and subsequent calcium (Ca2+) release. Released intracellular Ca2+ was reported to mediate TLR4 trafficking and subsequent activation of IRF3. [Aki D et al 2008; Chiang CY et al 2012].
			R-HSA-2201316 (Reactome)	TIRAP/Mal-deficient mice showed normal responses to the TLR3, TLR5, TLR7, and TLR9 ligands, but were defective in TLR4 and TLR2 ligand-induced proinflammatory cytokine production (Horng et al. 2002,Yamamoto et al. 2002). In contrast, TLR4 ligand-induced activation of IRF-3 and expression of IFN-inducible genes were not impaired in TIRAP/Mal knockout macrophages or in mice lacking both MyD88 and TIRAP/Mal (Horng et al. 2002,Yamamoto et al. 2002). Thus, TIRAP/Mal is an essential adapter that is involved in the MyD88-dependent pathway via TLR4 and TLR2, but not in the MyD88-independent pathway. Mal contains a phosphatidylinositol 4,5-bisphosphate-binding domain required for retention in the plasma membrane. The intracellular TIR domains of TLR2 or 4 associate with Mal at the cytoplasmic side of the plasma membrane, which in turn facilitates the binding of MyD88 to the activated TLR, leading to NF-kB and MAPK activation [Nunez Miguel et al 2007].
			R-HSA-2201341 (Reactome)	TRIF-related adapter molecule (TRAM or also known as TICAM2) is a sorting adapter which recruits TRIF to activated TLR4. Like TLR4, TRAM was detected both at the plasma membrane and in the endosomal compartment. TRAM was reported to recruit TRIF to the plasma membrane [Tanimuro N et al 2008]. However, TRAM did not induce TRIF-mediated signaling from the cell surface, instead, TRAM endocytosis was required for activation of IRF3 and induction of IFN-beta [Tanimuro N et al 2008; Kagan JC et al 2008]. Although, endocytosis of both TLR4 and TRAM and their association are required to trigger TRIF-mediated signaling, TRAM can target endosomes independently on its interaction with TLR4. TRAM cellular localization is controlled by myristoylation and phosphorylation of its N-terminal bipartite sorting signal motif [Kagan JC et al 2008]. TRAM has been shown to undergo phosphorylation on Ser-16 by protein kinase C epsilon in LPS-treated human THP1 and murine embryonic fibroblasts (MEF) cells [McGettrick AF et al 2006].
			R-HSA-2559439 (Reactome)	Upon LPS stimulation, CD14, in addition to promote endotoxin transfer to TLR4, also triggers complement receptor 3 (CR3) activation [Troelstra A et al 1999; Kagan JC and Medzithov R 2007]. LPS-mediated CR3 upregulation results in induction of PIP5K-dependent de novo synthesis of PIP2 in the lipid rafts through the phosphorylation of PI(4)P. Mal(TIRAP) is then recruited at the site of the newly generated PIP2 where it binds TLR4 via the TIR domain. Finally, MyD88 is recruited to the activated TLR4-CD14 complex via the TIRAP molecule and initiates a signaling cascade leading to a first wave of NF-kB activation from the plasma membrane [Kagan JC and Medzithov R 2007]. CR3 (CD11b/CD18) is a member of CD18 receptor family of cell surface glycoproteins, which are expressed in human phagocytes. Each of the three receptors (CR3, lymphocyte function-associated antigen LFA-1, and p150-95) is a heterodimer composed of a beta-chain (CD18) that is identical in all three receptors and a noncovalently associated alpha chain (CD11) that is unique to each molecule [ . CR3 is known as a receptor for the surface-bound complement protein C3bi, but it has been also reported to recognize several other ligands, including bacterial patterns such as LPS and lipid A. Two distinct binding sites on CR3 have been described: 1) a protein-binding-site that binds C3bi, fibrinogen, and Leishmania glycoprotein 63, and 2) a lipid- binding-site involved in the binding of LPS, lipid A [Wright SD et al 1989; Van Strijp J.A.G et al 1993]. CR3, LFA-1 and p150-95 have been reported to mediate not only LPS interaction but also promote the binding of Escherichia coli to human macrophages [Wright SD and Jong MTC 1986].
			R-HSA-2559456 (Reactome)	Upon LPS stimulation, Mal(TIRAP) was shown to bind to PIP2-rich regions on the cell surface trough its phosphatidylinositol 4,5-bisphosphate-binding domain [Kagan JC and Medzithov R 2007]. TLR2 or 4 associates with Mal(TIRAP) on the cell surface, which in turn facilitates the binding of MyD88 to the activated TLR, leading to NF-kB and MAPK activation [Nunez Miguel R et al 2007, Nagpal K et al 2009].
			R-HSA-2559464 (Reactome)	Scavenger receptor CD36 has been reported to function as an essential co-receptor involved in recognition of LTA and certain diacylated lipoproteins and presenting them to the TLR2:TLR6 heterodimer at the cell surface. CD14, a GPI-anchored molecule found on the cell surface of human phagocytes, has been also implicated in TLR2:TLR6 signaling [Stuart L et al 2005; Hoebe KP et al 2005; Triantafilou M et al 2006; Nilsen NJ et al 2008]
			R-HSA-2559468 (Reactome)	CD14, a GPI-anchored molecule found on the cell surface of human phagocytes, has been identified as a co-receptor that interacts with LPS. CD14 has been also implicated in TLR-2 signalling [Hajishengallis G et al 2006; Zivkovic A et al 2011]. Studies have demonstrated that CD14 can bind to triacylated lipoproteins and mediate the activation of the innate immune system trough TLR2:TLR1 complex [Nakata T et al 2006; Manukyan M et al 2005; Triantafilou M et al 2006]
RP105:MD1		TBar	R-HSA-166041 (Reactome)
TIRAP			R-HSA-2559456 (Reactome)
	TLR10 homodimer bound to ligand	Arrow	R-HSA-168947 (Reactome)
TLR10			R-HSA-168947 (Reactome)
	TLR1:TLR2 ligand:CD14	Arrow	R-HSA-2559468 (Reactome)
TLR1:TLR2 ligand:CD14			R-HSA-168951 (Reactome)
TLR1:TLR2 recognized ligand			R-HSA-2559468 (Reactome)
	TLR1:TLR2:TLR1/2 ligand:CD14	Arrow	R-HSA-168951 (Reactome)
TLR1:TLR2			R-HSA-168951 (Reactome)
TLR3			R-HSA-168092 (Reactome)
	TLR4:LY96:LPS:CD14	Arrow	R-HSA-166041 (Reactome)
	TLR4:LY96:LPS:CD14	Arrow	R-HSA-2201293 (Reactome)
TLR4:LY96:LPS:CD14			R-HSA-166168 (Reactome)
TLR4:LY96:LPS:CD14			R-HSA-2201293 (Reactome)
TLR4:LY96			R-HSA-166041 (Reactome)
	TLR5 homodimer:bacterial flagellin	Arrow	R-HSA-188025 (Reactome)
TLR5			R-HSA-188025 (Reactome)
	TLR6/2 ligand:CD14:CD36	Arrow	R-HSA-2559464 (Reactome)
TLR6/2 ligand:CD14:CD36			R-HSA-168950 (Reactome)
TLR6:TLR2 recognized ligand			R-HSA-2559464 (Reactome)
	TLR6:TLR2:ligand:CD14:CD36	Arrow	R-HSA-168950 (Reactome)
TLR6:TLR2			R-HSA-168950 (Reactome)
	TLR7 or TLR8:recognized ligand	Arrow	R-HSA-167983 (Reactome)
TLR7 or TLR8			R-HSA-167983 (Reactome)
TLR9			R-HSA-1679589 (Reactome)
	TRAM:TLR4:LY96:LPS:CD14	Arrow	R-HSA-166168 (Reactome)
Unmethylated CpG DNA			R-HSA-1679098 (Reactome)
Unmethylated CpG DNA			R-HSA-1679589 (Reactome)
Unmethylated CpG DNA			R-HSA-187895 (Reactome)
Viral dsRNA (-) stranded			R-HSA-168092 (Reactome)
ZFYVE20		Arrow	R-HSA-188002 (Reactome)
	activated TLR9:PI3K class III	Arrow	R-HSA-188002 (Reactome)
	fl-TLR9:unmethylated CpG DNA	Arrow	R-HSA-1679589 (Reactome)
	viral dsRNA :TLR3	Arrow	R-HSA-168092 (Reactome)