Mal, more than a bridge to MyD88

IUBMB Life

Volumn 65, Issue 9, 2013, Pages 777-786

  Bernard, Nicholas J ^a   O'Neill, Luke A ^a  

^a TRINITY COLLEGE DUBLIN   (Ireland)

Author keywords

genetic variation; Mal; PI3 kinase; protein function; signal transduction; signaling; TIRAP

Indexed keywords

ADVANCED GLYCATION END PRODUCT; BRUTON TYROSINE KINASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLAMMASOME; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 1BETA; INTERLEUKIN 1BETA CONVERTING ENZYME; INTERLEUKIN 6; MYD88 ADAPTOR LIKE PROTEIN; MYELOID DIFFERENTIATION FACTOR 88; PHOSPHATIDYLINOSITOL 4,5 BISPHOSPHATE; PROTEIN KINASE C; SUPPRESSOR OF CYTOKINE SIGNALING 1; TOLL LIKE RECEPTOR; TOLL LIKE RECEPTOR 1; TOLL LIKE RECEPTOR 2; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 7; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UNCLASSIFIED DRUG;

BACTERIAL CELL WALL; BACTERIAL COLONIZATION; BACTERIAL GROWTH; BACTERIAL INFECTION; BACTERIAL VIRULENCE; CRYSTAL STRUCTURE; DISEASE ASSOCIATION; GASTRITIS; GENE EXPRESSION; GENE LINKAGE DISEQUILIBRIUM; GENE MUTATION; GENETIC VARIABILITY; HUMAN; IMMUNE RESPONSE; IMMUNITY; IMMUNOPATHOLOGY; INFLAMMATORY DISEASE; MACROPHAGE; NONHUMAN; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; REVIEW; SALMONELLA ENTERICA; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; STOMACH CANCER; SYSTEMIC INFLAMMATORY RESPONSE SYNDROME; TRANSACTIVATION; TUBERCULOSIS; TULAREMIA; VACCINATION; VACCINE FAILURE;

GENETIC VARIATION; MAL; PI3-KINASE; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; SIGNALING; TIRAP;

ANIMALS; BACTERIAL INFECTIONS; HUMANS; IMMUNITY, CELLULAR; INFLAMMASOMES; MEMBRANE GLYCOPROTEINS; MYELOID DIFFERENTIATION FACTOR 88; NF-KAPPA B; RECEPTORS, INTERLEUKIN-1; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 2;

EID: 84883208257     PISSN: 15216543     EISSN: 15216551     Source Type: Journal    
DOI: 10.1002/iub.1201     Document Type: Review

References (100)

1. Poltorak, A., He, X., Smirnova, I., Liu, M. Y., and, Van Huffel, C., (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085-2088.
2. Hayashi, F., Smith, K. D., Ozinsky, A., Hawn, T. R., and, Yi, E. C., (2001) The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099-1103.
3. Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., and, Sato, S., (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745.
4. Jin, M. S., Kim, S. E., Heo, J. Y., Lee, M. E., and, Kim, H. M., (2007) Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 130, 1071-1082.
5. Kang, J. Y., Nan, X., Jin, M. S., Youn, S. J., and, Ryu, Y. H., (2009) Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity 31, 873-884.
6. Zhang, D., Zhang, G., Hayden, M. S., Greenblatt, M. B., and, Bussey, C., (2004) A toll-like receptor that prevents infection by uropathogenic bacteria. Science 303, 1522-1526.
7. Oldenburg, M., Kruger, A., Ferstl, R., Kaufmann, A., and, Nees, G., (2012) TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification. Science 337, 1111-1115.
8. Alexopoulou, L., Holt, A. C., Medzhitov, R., and, Flavell, R. A., (2001) Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 413, 732-738.
9. Lund, J. M., Alexopoulou, L., Sato, A., Karow, M., and, Adams, N. C., (2004) Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc. Natl. Acad. Sci. USA 101, 5598-5603.
10. Troutman, T. D., Hu, W., Fulenchek, S., Yamazaki, T., and, Kurosaki, T., (2012) Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt. Proc. Natl. Acad. Sci. USA 109, 273-278.
11. Ni, M., MacFarlane A. Wt, Toft, M., Lowell, C. A., and, Campbell, K. S., (2012) B-cell adaptor for PI3K (BCAP) negatively regulates Toll-like receptor signaling through activation of PI3K. Proc. Natl. Acad. Sci. USA 109, 267-272.
12. Fitzgerald, K. A., Palsson-McDermott, E. M., Bowie, A. G., Jefferies, C. A., and, Mansell, A. S., (2001) Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413, 78-83.
13. Horng, T., Barton, G. M., and, Medzhitov, R., (2001) TIRAP: an adapter molecule in the Toll signaling pathway. Nat. Immunol. 2, 835-841.
14. Horng, T., Barton, G. M., Flavell, R. A., and, Medzhitov, R., (2002) The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors. Nature 420, 329-333.
15. Yamamoto, M., Sato, S., Hemmi, H., Sanjo, H., and, Uematsu, S., (2002) Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature 420, 324-329.
16. Kenny, E. F., Talbot, S., Gong, M., Golenbock, D. T., and, Bryant, C. E., (2009) MyD88 adaptor-like is not essential for TLR2 signaling and inhibits signaling by TLR3. J. Immunol. 183, 3642-3651.
17. Cole, L. E., Laird, M. H., Seekatz, A., Santiago, A., and, Jiang, Z., (2010) Phagosomal retention of Francisella tularensis results in TIRAP/Mal-independent TLR2 signaling. J. Leukoc. Biol. 87, 275-281.
18. Kennedy, C. L., Najdovska, M., Tye, H., McLeod, L., and, Yu, L., (2013) Differential role of MyD88 and Mal/TIRAP in TLR2-mediated gastric tumourigenesis. Oncogene.
19. Erridge, C., Bennett-Guerrero, E., and, Poxton, I. R., (2002) Structure and function of lipopolysaccharides. Microbes Infect. 4, 837-851.
20. Gay, N. J., Gangloff, M., and, O'Neill, L. A., (2011) What the Myddosome structure tells us about the initiation of innate immunity. Trends Immunol. 32, 104-109.
21. Lin, S. C., Lo, Y. C., and, Wu, H., (2010) Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature 465, 885-890.
22. Cao, Z., Xiong, J., Takeuchi, M., Kurama, T., and, Goeddel, D. V., (1996) TRAF6 is a signal transducer for interleukin-1. Nature 383, 443-446.
23. Nyman, T., Stenmark, P., Flodin, S., Johansson, I., and, Hammarstrom, M., (2008) The crystal structure of the human toll-like receptor 10 cytoplasmic domain reveals a putative signaling dimer. J. Biol. Chem. 283, 11861-11865.
24. Ohnishi, H., Tochio, H., Kato, Z., Orii, K. E., and, Li, A., (2009) Structural basis for the multiple interactions of the MyD88 TIR domain in TLR4 signaling. Proc. Natl. Acad. Sci. USA 106, 10260-10265.
25. Khan, J. A., Brint, E. K., O'Neill, L. A., and, Tong, L., (2004) Crystal structure of the Toll/interleukin-1 receptor domain of human IL-1RAPL. J. Biol. Chem. 279, 31664-31670.
26. Valkov, E., Stamp, A., Dimaio, F., Baker, D., and, Verstak, B., (2011) Crystal structure of Toll-like receptor adaptor MAL/TIRAP reveals the molecular basis for signal transduction and disease protection. Proc. Natl. Acad. Sci. USA 108, 14879-14884.
27. Lin, Z., Lu, J., Zhou, W., and, Shen, Y., (2012) Structural insights into TIR domain specificity of the bridging adaptor Mal in TLR4 signaling. PLoS One 7, e34202.
28. Kagan, J. C., and, Medzhitov, R., (2006) Phosphoinositide-mediated adaptor recruitment controls Toll-like receptor signaling. Cell 125, 943-955.
29. Aksoy, E., Taboubi, S., Torres, D., Delbauve, S., and, Hachani, A., (2012) The p110delta isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock. Nat. Immunol. 13, 1045-1054.
30. Fruman, D. A., Snapper, S. B., Yballe, C. M., and, Alt, F. W., (1999) Phosphoinositide 3-kinase knockout mice: role of p85alpha in B cell development and proliferation. Biochem. Soc. Trans. 27, 624-629.
31. Fruman, D. A., Snapper, S. B., Yballe, C. M., Davidson, L., and, Yu, J. Y., (1999) Impaired B cell development and proliferation in absence of phosphoinositide 3-kinase p85alpha. Science 283, 393-397.
32. Arbibe, L., Mira, J. P., Teusch, N., Kline, L., and, Guha, M., (2000) Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway. Nat. Immunol. 1, 533-540.
33. Perona, R., Montaner, S., Saniger, L., Sanchez-Perez, I., and, Bravo, R., (1997) Activation of the nuclear factor-kappaB by Rho, CDC42, and Rac-1 proteins. Genes Dev. 11, 463-475.
34. Jefferies, C. A., and, O'Neill, L. A., (2000) Rac1 regulates interleukin 1-induced nuclear factor kappaB activation in an inhibitory protein kappaBalpha-independent manner by enhancing the ability of the p65 subunit to transactivate gene expression. J. Biol. Chem. 275, 3114-3120.
35. Santos-Sierra, S., Deshmukh, S. D., Kalnitski, J., Kuenzi, P., and, Wymann, M. P., (2009) Mal connects TLR2 to PI3Kinase activation and phagocyte polarization. EMBO J. 28, 2018-2027.
36. Sanlioglu, S., Williams, C. M., Samavati, L., Butler, N. S., and, Wang, G., (2001) Lipopolysaccharide induces Rac1-dependent reactive oxygen species formation and coordinates tumor necrosis factor-alpha secretion through IKK regulation of NF-kappa B. J. Biol. Chem. 276, 30188-3098.
37. Equils, O., Madak, Z., Liu, C., Michelsen, K. S., and, Bulut, Y., (2004) Rac1 and Toll-IL-1 receptor domain-containing adapter protein mediate Toll-like receptor 4 induction of HIV-long terminal repeat. J. Immunol. 2004, 172,7642-7646.
38. Mansell, A., Brint, E., Gould, J. A., O'Neill, L. A., and, Hertzog, P. J., (2004) Mal interacts with tumor necrosis factor receptor-associated factor (TRAF)-6 to mediate NF-kappaB activation by toll-like receptor (TLR)-2 and TLR4. J. Biol. Chem. 279, 37227-37230.
39. Verstak, B., Nagpal, K., Bottomley, S. P., Golenbock, D. T., and, Hertzog, P. J., (2009) MyD88 adapter-like (Mal)/TIRAP interaction with TRAF6 is critical for TLR2- and TLR4-mediated NF-kappaB proinflammatory responses. J. Biol. Chem. 284, 24192-24203.
40. Mukhopadhyay, S., Mohanty, M., Mangla, A., George, A., and, Bal, V., (2002) Macrophage effector functions controlled by Bruton's tyrosine kinase are more crucial than the cytokine balance of T cell responses for microfilarial clearance. J. Immunol. 168, 2914-2921.
41. Jefferies, C. A., Doyle, S., Brunner, C., Dunne, A., and, Brint, E., (2003) Bruton's tyrosine kinase is a Toll/interleukin-1 receptor domain-binding protein that participates in nuclear factor kappaB activation by Toll-like receptor 4. J. Biol. Chem. 278, 26258-26264.
42. Gray, P., Dunne, A., Brikos, C., Jefferies, C. A., and, Doyle, S. L., (2006) MyD88 adapter-like (Mal) is phosphorylated by Bruton's tyrosine kinase during TLR2 and TLR4 signal transduction. J. Biol. Chem. 281, 10489-10495.
43. Mansell, A., Smith, R., Doyle, S. L., Gray, P., and, Fenner, J. E., (2006) Suppressor of cytokine signaling 1 negatively regulates Toll-like receptor signaling by mediating Mal degradation. Nat. Immunol. 7, 148-155.
44. Montminy, M. R., and, Bilezikjian, L. M., (1987) Binding of a nuclear protein to the cyclic-AMP response element of the somatostatin gene. Nature 328, 175-178.
45. O'Donnell, P. M., and, Taffet, S. M., (2002) The proximal promoter region is essential for lipopolysaccharide induction and cyclic AMP inhibition of mouse tumor necrosis factor-alpha. J. Interferon Cytokine Res. 22, 539-548.
46. Eliopoulos, A. G., Dumitru, C. D., Wang, C. C., Cho, J., and, Tsichlis, P. N., (2002) Induction of COX-2 by LPS in macrophages is regulated by Tpl2-dependent CREB activation signals. EMBO J. 21, 4831-4840.
47. Platzer, C., Fritsch, E., Elsner, T., Lehmann, M. H., and, Volk, H. D., (1999) Cyclic adenosine monophosphate-responsive elements are involved in the transcriptional activation of the human IL-10 gene in monocytic cells. Eur. J. Immunol. 29, 3098-3104.
48. Mellett, M., Atzei, P., Jackson, R., O'Neill, L. A., and, Moynagh, P. N., (2011) Mal mediates TLR-induced activation of CREB and expression of IL-10. J. Immunol. 186, 4925-4935.
49. Miggin, S. M., Palsson-McDermott, E., Dunne, A., Jefferies, C., and, Pinteaux, E., (2007) NF-kappaB activation by the Toll-IL-1 receptor domain protein MyD88 adapter-like is regulated by caspase-1. Proc. Natl. Acad. Sci. USA 104, 3372-3377.
50. Nunez Miguel, R., Wong, J., Westoll, J. F., Brooks, H. J., and, O'Neill, L. A., (2007) A dimer of the Toll-like receptor 4 cytoplasmic domain provides a specific scaffold for the recruitment of signalling adaptor proteins. PLoS One 2, e788.
51. Ulrichts, P., Bovijn, C., Lievens, S., Beyaert, R., and, Tavernier, J., (2010) Caspase-1 targets the TLR adaptor Mal at a crucial TIR-domain interaction site. J. Cell. Sci. 123 (Part 2), 256-265.
52. Rebsamen, M., Meylan, E., Curran, J., and, Tschopp, J., (2008) The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases. Cell Death Differ. 15, 1804-1811.
53. Dunne, A., Carpenter, S., Brikos, C., Gray, P., and, Strelow, A., (2010) IRAK1 and IRAK4 promote phosphorylation, ubiquitination, and degradation of MyD88 adaptor-like (Mal). J. Biol. Chem. 285, 18276-18282.
54. Johnson, A. C., Li, X., and, Pearlman, E., (2008) MyD88 functions as a negative regulator of TLR3/TRIF-induced corneal inflammation by inhibiting activation of c-Jun N-terminal kinase. J. Biol. Chem. 283, 3988-3996.
55. Sakaguchi, M., Murata, H., Yamamoto, K., Ono, T., and, Sakaguchi, Y., (2011) TIRAP, an adaptor protein for TLR2/4, transduces a signal from RAGE phosphorylated upon ligand binding. PLoS One 6, e23132.
56. Kislinger, T., Fu, C., Huber, B., Qu, W., and, Taguchi, A., (1999) N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. J. Biol. Chem. 274, 31740-31749.
57. Hori, O., Brett, J., Slattery, T., Cao, R., and, Zhang, J., (1995) The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system. J. Biol. Chem. 270, 25752-25761.
58. Yan, S. D., Zhu, H., Zhu, A., Golabek, A., and, Du, H., (2000) Receptor-dependent cell stress and amyloid accumulation in systemic amyloidosis. Nat. Med. 6, 643-651.
59. Moroz, O. V., Antson, A. A., Dodson, E. J., Burrell, H. J., and, Grist, S. J., (2002) The structure of S100A12 in a hexameric form and its proposed role in receptor signalling. Acta Crystallogr. D Biol. Crystallogr. 58 (Part 3), 407-413.
60. Newman, R. M., Salunkhe, P., Godzik, A., and, Reed, J. C., (2006) Identification and characterization of a novel bacterial virulence factor that shares homology with mammalian Toll/interleukin-1 receptor family proteins. Infect. Immun. 74, 594-601.
61. Cirl, C., Wieser, A., Yadav, M., Duerr, S., and, Schubert, S., (2008) Subversion of Toll-like receptor signaling by a unique family of bacterial Toll/interleukin-1 receptor domain-containing proteins. Nat. Med. 14, 399-406.
62. Radhakrishnan, G. K., Yu, Q., Harms, J. S., and, Splitter, G. A., (2009) Brucella TIR domain-containing protein mimics properties of the Toll-like receptor adaptor protein TIRAP. J. Biol. Chem. 284, 9892-9898.
63. Sengupta, D., Koblansky, A., Gaines, J., Brown, T., and, West, A. P., (2010) Subversion of innate immune responses by Brucella through the targeted degradation of the TLR signaling adapter, MAL. J. Immunol. 184, 956-964.
64. Jeyaseelan, S., Manzer, R., Young, S. K., Yamamoto, M., and, Akira, S., (2005) Toll-IL-1 receptor domain-containing adaptor protein is critical for early lung immune responses against Escherichia coli lipopolysaccharide and viable Escherichia coli. J. Immunol. 175, 7484-7495.
65. Jeyaseelan, S., Young, S. K., Yamamoto, M., Arndt, P. G., and, Akira, S., (2006) Toll/IL-1R domain-containing adaptor protein (TIRAP) is a critical mediator of antibacterial defense in the lung against Klebsiella pneumoniae but not Pseudomonas aeruginosa. J. Immunol. 177, 538-547.
66. Jerke, S., Srinivasan, A., and, McSorley, S. J., (2008) Expression of Toll/IL-1R domain-containing adaptor protein (TIRAP) is detrimental to primary clearance of Salmonella and is not required for the generation of protective immunity. Immunol. Lett. 116, 64-71.
67. Talbot, S., Totemeyer, S., Yamamoto, M., Akira, S., and, Hughes, K., (2009) Toll-like receptor 4 signalling through MyD88 is essential to control Salmonella enterica serovar typhimurium infection, but not for the initiation of bacterial clearance. Immunology 128, 472-483.
68. Corr, S. C., Palsson-McDermott, E. M., Grishina, I., Barry, S. P., and, Aviello, G., (2013) MyD88 adaptor-like (Mal) functions in the epithelial barrier and contributes to intestinal integrity via protein kinase C. Mucosal Immunol.
69. Goldblum, S. E., Ding, X., Brann, T. W., and, Campbell-Washington, J., (1993) Bacterial lipopolysaccharide induces actin reorganization, intercellular gap formation, and endothelial barrier dysfunction in pulmonary vascular endothelial cells: concurrent F-actin depolymerization and new actin synthesis. J. Cell. Physiol. 157, 13-23.
70. Bannerman, D. D., and, Goldblum, S. E., (1997) Endotoxin induces endothelial barrier dysfunction through protein tyrosine phosphorylation. Am. J. Physiol. 273 (1 Part 1), L217-L226.
71. Gong, P., Angelini, D. J., Yang, S., Xia, G., and, Cross, A. S., (2008) TLR4 signaling is coupled to SRC family kinase activation, tyrosine phosphorylation of zonula adherens proteins, and opening of the paracellular pathway in human lung microvascular endothelia. J. Biol. Chem. 283, 13437-13449.
72. Pai, A. B., Patel, H., Prokopienko, A. J., Alsaffar, H., and, Gertzberg, N., (2012) Lipoteichoic acid from Staphylococcus aureus induces lung endothelial cell barrier dysfunction: role of reactive oxygen and nitrogen species. PLoS One 7, e49209.
73. Liu, A., Gong, P., Hyun, S. W., Wang, K. Z., and, Cates, E. A., (2012) TRAF6 protein couples Toll-like receptor 4 signaling to Src family kinase activation and opening of paracellular pathway in human lung microvascular endothelia. J. Biol. Chem. 287, 16132-16145.
74. Stuart, R. O., and, Nigam, S. K., (1995) Regulated assembly of tight junctions by protein kinase C. Proc. Natl. Acad. Sci. USA 92, 6072-6076.
75. Jain, S., Suzuki, T., Seth, A., Samak, G., and, Rao, R., (2011) Protein kinase Czeta phosphorylates occludin and promotes assembly of epithelial tight junctions. Biochem. J. 437, 289-299.
76. Koizumi, J., Kojima, T., Ogasawara, N., Kamekura, R., and, Kurose, M., (2008) Protein kinase C enhances tight junction barrier function of human nasal epithelial cells in primary culture by transcriptional regulation. Mol. Pharmacol. 74, 432-442.
77. Clarke, H., Soler, A. P., and, Mullin, J. M., (2000) Protein kinase C activation leads to dephosphorylation of occludin and tight junction permeability increase in LLC-PK1 epithelial cell sheets. J. Cell. Sci. 113 (Part 18), 3187-3196.
78. Mullin, J. M., Laughlin, K. V., Ginanni, N., Marano, C. W., and, Clarke, H. M., (2000) Increased tight junction permeability can result from protein kinase C activation/translocation and act as a tumor promotional event in epithelial cancers. Ann. NY Acad. Sci. 915, 231-236.
79. Nagpal, K., Plantinga, T. S., Wong, J., Monks, B. G., and, Gay, N. J., (2009) A TIR domain variant of MyD88 adapter-like (Mal)/TIRAP results in loss of MyD88 binding and reduced TLR2/TLR4 signaling. J. Biol. Chem. 284, 25742-25748.
80. George, J., Kubarenko, A. V., Rautanen, A., Mills, T. C., and, Colak, E., (2010) MyD88 adaptor-like D96N is a naturally occurring loss-of-function variant of TIRAP. J. Immunol. 184, 3025-3032.
81. Zhang, Y. X., Xue, Y., Liu, J. Y., Zhao, M. Y., and, Li, F. J., (2011) Association of TIRAP (MAL) gene polymorhisms with susceptibility to tuberculosis in a Chinese population. Genet. Mol. Res. 10, 7-15.
82. Khor, C. C., Chapman, S. J., Vannberg, F. O., Dunne, A., and, Murphy, C., (2007) A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis. Nat. Genet. 39, 523-528.
83. Ferwerda, B., Alonso, S., Banahan, K., McCall, M. B., and, Giamarellos-Bourboulis, E. J., (2009) Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock. Proc. Natl. Acad. Sci. USA 106, 10272-10277.
84. Nejentsev, S., Thye, T., Szeszko, J. S., Stevens, H., and, Balabanova, Y., (2008) Analysis of association of the TIRAP (MAL) S180L variant and tuberculosis in three populations. Nat. Genet. 40, 261-262;authorreply262-263.
85. Castiblanco, J., Varela, D. C., Castano-Rodriguez, N., Rojas-Villarraga, A., and, Hincapie, M. E., (2008) TIRAP (MAL) S180L polymorphism is a common protective factor against developing tuberculosis and systemic lupus erythematosus. Infect. Genet. Evol. 8, 541-544.
86. Miao, R., Li, J., Sun, Z., Xu, F., and, Shen, H., (2011) Meta-analysis on the association of TIRAP S180L variant and tuberculosis susceptibility. Tuberculosis (Edinb) 91, 268-272.
87. Durrani, O., Banahan, K., Sheedy, F. J., McBride, L., and, Ben-Chetrit, E., (2011) TIRAP Ser180Leu polymorphism is associated with Behcet's disease. Rheumatology (Oxford) 50, 1760-1765.
88. Papadopoulos, A. I., Ferwerda, B., Antoniadou, A., Sakka, V., and, Galani, L., (2012) Association of Mal/TIRAP S180L variant polymorphism with decreased infection risk in patients with advanced HIV-1 infection. Cytokine 60, 104-107.
89. Ramasawmy, R., Cunha-Neto, E., Fae, K. C., Borba, S. C., and, Teixeira, P. C., (2009) Heterozygosity for the S180L variant of MAL/TIRAP, a gene expressing an adaptor protein in the Toll-like receptor pathway, is associated with lower risk of developing chronic Chagas cardiomyopathy. J. Infect. Dis. 199, 1838-1845.
90. Sheedy, F. J., Marinou, I., O'Neill, L. A., and, Wilson, A. G., (2008) The Mal/TIRAP S180L and TLR4 G299D polymorphisms are not associated with susceptibility to, or severity of, rheumatoid arthritis. Ann. Rheum. Dis. 67, 1328-1331.
91. Ladhani, S. N., Davila, S., Hibberd, M. L., Heath, P. T., and, Ramsay, M. E., (2010) Association between single-nucleotide polymorphisms in Mal/TIRAP and interleukin-10 genes and susceptibility to invasive haemophilus influenzae serotype b infection in immunized children. Clin. Infect. Dis. 51, 761-767.
92. von Bernuth, H., Picard, C., Jin, Z., Pankla, R., and, Xiao, H., (2008) Pyogenic bacterial infections in humans with MyD88 deficiency. Science 321, 691-696.
93. Muzio, M., Ni, J., Feng, P., and, Dixit, V. M., (1997) IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278, 1612-1615.
94. Yamagata, M., Merlie, J. P., and, Sanes, J. R., (1994) Interspecific comparisons reveal conserved features of the Drosophila Toll protein. Gene 139, 223-228.
95. Hultmark, D., (1994) Macrophage differentiation marker MyD88 is a member of the Toll/IL-1 receptor family. Biochem. Biophys. Res. Commun. 199, 144-146.
96. Wesche, H., Henzel, W. J., Shillinglaw, W., Li, S., and, Cao, Z., (1997) MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7, 837-847.
97. Adachi, O., Kawai, T., Takeda, K., Matsumoto, M., and, Tsutsui, H., (1998) Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9, 143-150.
98. Kroeger, K. M., Sullivan, B. M., and, Locksley, R. M., (2009) IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38alpha-dependent pathway. J. Leukoc. Biol. 86, 769-778.
99. Sun, D., and, Ding, A., (2006) MyD88-mediated stabilization of interferon-gamma-induced cytokine and chemokine mRNA. Nat. Immunol. 7, 375-381.
100. Marek, L. R., and, Kagan, J. C., (2012) Phosphoinositide binding by the Toll adaptor dMyD88 controls antibacterial responses in Drosophila. Immunity 36, 612-622.