Genome-wide expression profiling and mutagenesis studies reveal that lipopolysaccharide responsiveness appears to be absolutely dependent on TLR4 and MD-2 expression and is dependent upon intermolecular ionic interactions

Journal of Immunology

Volumn 187, Issue 7, 2011, Pages 3683-3693

  Meng, Jianmin ^a   Gong, Mei ^a   Björkbacka, Harry ^b   Golenbock, Douglas T ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b LUND UNIVERSITY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; ENDOTOXIN; LIPID A; LIPOPOLYSACCHARIDE; MYELOID DIFFERENTIATION FACTOR 88; PHOSPHATE; PROTEIN MD 2; TOLL LIKE RECEPTOR 4;

ANIMAL CELL; ARTICLE; CELL STIMULATION; COMPLEX FORMATION; COMPUTER MODEL; CONTROLLED STUDY; CRYSTAL STRUCTURE; GENE EXPRESSION PROFILING; GENE INDUCTION; GENE REPRESSION; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IONIC INTERACTION; MACROPHAGE; MOLECULAR GENETICS; MOLECULAR INTERACTION; MOUSE; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; WILD TYPE;

ANIMALS; BONE MARROW CELLS; CELL SEPARATION; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; GENE EXPRESSION PROFILING; GENOME-WIDE ASSOCIATION STUDY; IMMUNOBLOTTING; IMMUNOPRECIPITATION; LIPOPOLYSACCHARIDES; LYMPHOCYTE ANTIGEN 96; MICE; MODELS, MOLECULAR; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTOR 4;

EID: 80053487700     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1101397     Document Type: Article

References (57)

1. Janeway, C. A., Jr., and R. Medzhitov. 2002. Innate immune recognition. Annu. Rev. Immunol. 20: 197-216. (Pubitemid 34293424)
2. Rangel-Frausto,M. S. 2005. Sepsis: still going strong. Arch. Med. Res. 36: 672-681. (Pubitemid 41436236)
3. Natanson, C., W. D. Hoffman, A. F. Suffredini, P. Q. Eichacker, and R. L. Danner. 1994. Selected treatment strategies for septic shock based on proposed mechanisms of pathogenesis. Ann. Intern. Med. 120: 771-783. (Pubitemid 24125299)
4. Cohen, J., and M. P. Glauser. 1991. Septic shock: treatment. Lancet 338: 736-739.
5. Zasloff, M. 2002. Antimicrobial peptides of multicellular organisms. Nature 415: 389-395. (Pubitemid 34100944)
6. Spek, C. A., A. Verbon, H. Aberson, J. P. Pribble, C. J. McElgunn, T. Turner, T. Axtelle, J. Schouten, T. Van Der Poll, and P. H. Reitsma. 2003. Treatment with an anti-CD14 monoclonal antibody delays and inhibits lipopolysaccharide-induced gene expression in humans in vivo. J. Clin. Immunol. 23: 132-140. (Pubitemid 36324203)
7. Richards, G., H. Levy, P. F. Laterre, C. Feldman, B. Woodward, B. M. Bates, and R. L. Qualy. 2011. CURB-65, PSI, and APACHE II to assess mortality risk in patients with severe sepsis and community acquired pneumonia in PROWESS. J. Intensive Care Med. 26: 34-40.
8. Poltorak, A., P. Ricciardi-Castagnoli, S. Citterio, and B. Beutler. 2000. Physical contact between lipopolysaccharide and toll-like receptor 4 revealed by genetic complementation. Proc. Natl. Acad. Sci. USA 97: 2163-2167. (Pubitemid 30134039)
9. Randow, F., and B. Seed. 2001. Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability. Nat. Cell Biol. 3: 891-896. (Pubitemid 32952253)
10. Lien, E., T. K. Means, H. Heine, A. Yoshimura, S. Kusumoto, K. Fukase, M. J. Fenton, M. Oikawa, N. Qureshi, B. Monks, et al. 2000. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J. Clin. Invest. 105: 497-504. (Pubitemid 30127250)
11. Park, B. S., D. H. Song, H. M. Kim, B. S. Choi, H. Lee, and J. O. Lee. 2009. The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 458: 1191-1195.
12. Shimazu, R., S. Akashi, H. Ogata, Y. Nagai, K. Fukudome, K. Miyake, and M. Kimoto. 1999. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189: 1777-1782. (Pubitemid 29272694)
13. Medzhitov, R., and C. Janeway Jr. 2000. The Toll receptor family and microbial recognition. Trends Microbiol. 8: 452-456.
14. Medzhitov, R., and C. Janeway Jr. 2000. Innate immunity. N. Engl. J. Med. 343: 338-344.
15. Medzhitov, R., and C. Janeway Jr. 2000. Innate immune recognition: mechanisms and pathways. Immunol. Rev. 173: 89-97. (Pubitemid 30095213)
16. Akira, S., and K. Takeda. 2004. Toll-like receptor signalling. Nat. Rev. Immunol. 4: 499-511. (Pubitemid 38931765)
17. Moynagh, P. N. 2005. TLR signalling and activation of IRFs: revisiting old friends from the NF-kappaB pathway. Trends Immunol. 26: 469-476. (Pubitemid 41139256)
18. Kagan, J. C., T. Su, T. Horng, A. Chow, S. Akira, and R. Medzhitov. 2008. TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-beta. Nat. Immunol. 9: 361-368. (Pubitemid 351405105)
19. McGettrick, A. F., and L. A. O'Neill. 2010. Localisation and trafficking of Toll-like receptors: an important mode of regulation. Curr. Opin. Immunol. 22: 20-27.
20. Lu, Y. C., W. C. Yeh, and P. S. Ohashi. 2008. LPS/TLR4 signal transduction pathway. Cytokine 42: 145-151.
21. Kim, H. M., B. S. Park, J. I. Kim, S. E. Kim, J. Lee, S. C. Oh, P. Enkhbayar, N. Matsushima, H. Lee, O. J. Yoo, and J. O. Lee. 2007. Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 130: 906-917. (Pubitemid 47332573)
22. Resman, N., J. Vasl, A. Oblak, P. Pristovsek, T. L. Gioannini, J. P. Weiss, and R. Jerala. 2009. Essential roles of hydrophobic residues in both MD-2 and toll-like receptor 4 in activation by endotoxin. J. Biol. Chem. 284: 15052-15060.
23. Meng, J., E. Lien, and D. T. Golenbock. 2010. MD-2-mediated ionic interactions between lipid A and TLR4 are essential for receptor activation. J. Biol. Chem. 285: 8695-8702.
24. Qureshi, N., K. Takayama, and E. Ribi. 1982. Purification and structural determination of nontoxic lipid A obtained from the lipopolysaccharide of Salmonella typhimurium. J. Biol. Chem. 257: 11808-11815. (Pubitemid 13218648)
25. Rietschel, E. T., T. Kirikae, F. U. Schade, U. Mamat, G. Schmidt, H. Loppnow, A. J. Ulmer, U. Zähringer, U. Seydel, F. Di Padova, et al. 1994. Bacterial endotoxin: molecular relationships of structure to activity and function. FASEB J. 8: 217-225. (Pubitemid 24067145)
26. Rietschel, E. T., T. Kirikae, F. U. Schade, A. J. Ulmer, O. Holst, H. Brade, G. Schmidt, U. Mamat, H. D. Grimmecke, S. Kusumoto, et al. 1993. The chemical structure of bacterial endotoxin in relation to bioactivity. Immunobiology 187: 169-190. (Pubitemid 23150766)
27. Mata-Haro, V., C. Cekic, M. Martin, P. M. Chilton, C. R. Casella, and T. C. Mitchell. 2007. The vaccine adjuvant monophosphoryl lipid A as a TRIF-biased agonist of TLR4. Science 316: 1628-1632. (Pubitemid 46982038)
28. Chen, T. Y., S. W. Bright, J. L. Pace, S. W. Russell, and D. C. Morrison. 1990. Induction of macrophage-mediated tumor cytotoxicity by a hamster monoclonal antibody with specificity for lipopolysaccharide receptor. J. Immunol. 145: 8-12.
29. Couturier, C., N. Haeffner-Cavaillon, M. Caroff, and M. D. Kazatchkine. 1991. Binding sites for endotoxins (lipopolysaccharides) on human monocytes. J. Immunol. 147: 1899-1904.
30. Kirkland, T. N., G. D. Virca, T. Kuus-Reichel, F. K. Multer, S. Y. Kim, R. J. Ulevitch, and P. S. Tobias. 1990. Identification of lipopolysaccharide- binding proteins in 70Z/3 cells by photoaffinity cross-linking. J. Biol. Chem. 265: 9520-9525.
31. Golenbock, D. T., R. Y. Hampton, C. R. Raetz, and S. D. Wright. 1990. Human phagocytes have multiple lipid A-binding sites. Infect. Immun. 58: 4069-4075.
32. Wright, S. D., and M. T. Jong. 1986. Adhesion-promoting receptors on human macrophages recognize Escherichia coli by binding to lipopolysaccharide. J. Exp. Med. 164: 1876-1888. (Pubitemid 17217970)
33. Wright, S. D., P. S. Tobias, R. J. Ulevitch, and R. A. Ramos. 1989. Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages. J. Exp. Med. 170: 1231-1241. (Pubitemid 19250690)
34. Ingalls, R. R., and D. T. Golenbock. 1995. CD11c/CD18, a transmembrane signaling receptor for lipopolysaccharide. J. Exp. Med. 181: 1473-1479.
35. Haziot, A., N. Hijiya, S. C. Gangloff, J. Silver, and S. M. Goyert. 2001. Induction of a novel mechanism of accelerated bacterial clearance by lipopolysaccharide in CD14-deficient and Toll-like receptor 4-deficient mice. J. Immunol. 166: 1075-1078. (Pubitemid 32060265)
36. Nagai, Y., R. Shimazu, H. Ogata, S. Akashi, K. Sudo, H. Yamasaki, S. Hayashi, Y. Iwakura, M. Kimoto, and K. Miyake. 2002. Requirement for MD-1 in cell surface expression of RP105/CD180 and B-cell responsiveness to lipopolysaccharide. Blood 99: 1699-1705. (Pubitemid 34533044)
37. Lorenz, E., D. D. Patel, T. Hartung, and D. A. Schwartz. 2002. Toll-like receptor 4 (TLR4)-deficient murine macrophage cell line as an in vitro assay system to show TLR4-independent signaling of Bacteroides fragilis lipopolysaccharide. Infect. Immun. 70: 4892-4896.
38. Humphries, H. E., M. Triantafilou, B. L. Makepeace, J. E. Heckels, K. Triantafilou, and M. Christodoulides. 2005. Activation of human meningeal cells is modulated by lipopolysaccharide (LPS) and non-LPS components of Neisseria meningitidis and is independent of Toll-like receptor (TLR)4 and TLR2 signalling. Cell. Microbiol. 7: 415-430. (Pubitemid 40277921)
39. Kaneko, T., W. E. Goldman, P. Mellroth, H. Steiner, K. Fukase, S. Kusumoto, W. Harley, A. Fox, D. Golenbock, and N. Silverman. 2004. Monomeric and polymeric gram-negative peptidoglycan but not purified LPS stimulate the Drosophila IMD pathway. Immunity 20: 637-649. (Pubitemid 38638131)
40. Hirschfeld, M., Y. Ma, J. H. Weis, S. N. Vogel, and J. J. Weis. 2000. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J. Immunol. 165: 618-622. (Pubitemid 30484724)
41. Saal, L. H., C. Troein, J. Vallon-Christersson, S. Gruvberger, A. Borg, and C. Peterson. 2002. BioArray Software Environment (BASE): a platform for comprehensive management and analysis of microarray data. Genome Biol. 3: SOFTWARE0003.
42. Saeed, A. I., V. Sharov, J. White, J. Li, W. Liang, N. Bhagabati, J. Braisted, M. Klapa, T. Currier, M. Thiagarajan, et al. 2003. TM4: a free, open-source system for microarray data management and analysis. Biotechniques 34: 374-378. (Pubitemid 36184095)
43. Eichler, G. S., S. Huang, and D. E. Ingber. 2003. Gene Expression Dynamics Inspector (GEDI): for integrative analysis of expression profiles. Bioinformatics 19: 2321-2322. (Pubitemid 37483992)
44. Hosack, D. A., G. Dennis, Jr., B. T. Sherman, H. C. Lane, and R. A. Lempicki. 2003. Identifying biological themes within lists of genes with EASE. Genome Biol. 4: R70.
45. Fitzgerald, K. A., E. M. Palsson-McDermott, A. G. Bowie, C. A. Jefferies, A. S. Mansell, G. Brady, E. Brint, A. Dunne, P. Gray, M. T. Harte, et al. 2001. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 413: 78-83. (Pubitemid 32843491)
46. Schromm, A. B., E. Lien, P. Henneke, J. C. Chow, A. Yoshimura, H. Heine, E. Latz, B. G. Monks, D. A. Schwartz, K. Miyake, and D. T. Golenbock. 2001. Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling. J. Exp. Med. 194: 79-88. (Pubitemid 32660439)
47. Golenbock, D. T., R. Y. Hampton, N. Qureshi, K. Takayama, and C. R. Raetz. 1991. Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J. Biol. Chem. 266: 19490-19498. (Pubitemid 21908258)
48. Meng, J., J. R. Drolet, B. G. Monks, and D. T. Golenbock. 2010. MD-2 residues tyrosine 42, arginine 69, aspartic acid 122, and leucine 125 provide species specificity for lipid IVA. J. Biol. Chem. 285: 27935-27943.
49. Björkbacka, H., K. A. Fitzgerald, F. Huet, X. Li, J. A. Gregory, M. A. Lee, C. M. Ordija, N. E. Dowley, D. T. Golenbock, and M. W. Freeman. 2004. The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades. Physiol. Genomics 19: 319-330. (Pubitemid 40039937)
50. Nagai, Y., S. Akashi, M. Nagafuku, M. Ogata, Y. Iwakura, S. Akira, T. Kitamura, A. Kosugi, M. Kimoto, and K. Miyake. 2002. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nat. Immunol. 3: 667-672. (Pubitemid 34752476)
51. Dziarski, R., and D. Gupta. 2000. Role of MD-2 in TLR2- and TLR4-mediated recognition of Gram-negative and Gram-positive bacteria and activation of chemokine genes. J. Endotoxin Res. 6: 401-405. (Pubitemid 32241952)
52. Raetz, C. R., C. M. Reynolds, M. S. Trent, and R. E. Bishop. 2007. Lipid A modification systems in gram-negative bacteria. Annu. Rev. Biochem. 76: 295-329.
53. Dixon, D. R., and R. P. Darveau. 2005. Lipopolysaccharide heterogeneity: innate host responses to bacterial modification of lipid a structure. J. Dent. Res. 84: 584-595. (Pubitemid 43827837)
54. Montminy, S. W., N. Khan, S. McGrath, M. J.Walkowicz, F. Sharp, J. E. Conlon, K. Fukase, S. Kusumoto, C. Sweet, K. Miyake, et al. 2006. Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response. Nat. Immunol. 7: 1066-1073. (Pubitemid 44420651)
55. Raman, V. S., A. Bhatia, A. Picone, J. Whittle, H. R. Bailor, J. O'Donnell, S. Pattabhi, J. A. Guderian, R. Mohamath, M. S. Duthie, and S. G. Reed. 2010. Applying TLR synergy in immunotherapy: implications in cutaneous leishmaniasis. J Immunol. 185: 1701-1710.
56. Fox, C. B., M. Friede, S. G. Reed, and G. C. Ireton. 2010. Synthetic and natural TLR4 agonists as safe and effective vaccine adjuvants. Subcell. Biochem. 53: 303-321.
57. Fusco, W. G., G. Afonina, I. Nepluev, D. M. Cholon, N. Choudhary, P. A. Routh, G. W. Almond, P. E. Orndorff, H. Staats, M. M. Hobbs, et al. 2010. Immunization with the Haemophilus ducreyi hemoglobin receptor HgbA with adjuvant monophosphoryl lipid A protects swine from a homologous but not a heterologous challenge. Infect. Immun. 78: 3763-3772.