Innate immune sensing and its roots: The story of endotoxin

Nature Reviews Immunology

Volumn 3, Issue 2, 2003, Pages 169-176

  Beutler, Bruce ^a   Rietschel, Ernst Th ^b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b RESEARCH CENTER BORSTEL   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ENDOTOXIN; TOLL LIKE RECEPTOR; CELL SURFACE RECEPTOR; DROSOPHILA PROTEIN; LIPOPOLYSACCHARIDE; MEMBRANE PROTEIN;

BACTERIUM CULTURE; CELL CULTURE; GENETIC ANALYSIS; HOST RESISTANCE; HYPOTHESIS; IMMUNOSENSOR; INTOXICATION; LETHALITY; NONHUMAN; ORGANIC MATTER PRODUCTION; POLLUTION; PRIORITY JOURNAL; REVIEW; SOCIAL STATUS; BIOLOGICAL MODEL; HISTORY; IMMUNOLOGY; INNATE IMMUNITY; MACROPHAGE; SIGNAL TRANSDUCTION;

DROSOPHILA PROTEINS; ENDOTOXINS; HISTORY, 18TH CENTURY; HISTORY, 19TH CENTURY; HISTORY, 20TH CENTURY; HISTORY, ANCIENT; IMMUNITY, NATURAL; LIPOPOLYSACCHARIDES; MACROPHAGES; MEMBRANE GLYCOPROTEINS; MODELS, IMMUNOLOGICAL; RECEPTORS, CELL SURFACE; SIGNAL TRANSDUCTION; TOLL-LIKE RECEPTORS;

EID: 0037317763     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri1004     Document Type: Review

References (98)

1. Magendie, F. Remarques sur la notice pércédente (de Dupre), avec quelque expériences sur les effets des substances en putréfaction. J. Physiol. (Paris) 3, 61-86 (1823).
2. Westphal, O., Westphal, U. & Sommer, T. in Microbiology-1977 (ed. Schlessinger, D.) 221-238 (American Society of Microbiology, Washington DC, 1977).
3. Panum, P. L. Das putride Gift, die Bakterien, die putride Infektion oder Intoxikation und die Septikämie (The putrid poison, the bacteria, the putrid infection or intoxication and the septicaemia). Arch. Pathol. Anat. Physiol. Klin. Med. (Virchow's Arch.) 60, 301-382 (1874).
4. Bergmann, E. & Schmiedeberg, O. Ueber das schwefelsaure Sepsin (das Gift faulender Substanzen). Centralbl. Med. Wissenschaften 32, 497-498 (1868).
5. Henle, J. in Klassiker der Medizin Vol. 3 (ed. Sudhoff, K.) 1-88 (Joh, Ambrosius Barth, Leipzig, 1910).
6. Latour, B. Pasteur - Une Science, Un Style, Un Siècle (Libraire Académique, Perrin, Paris, 1994).
7. Brock, D. Th. Robert Koch. A Life in Medicine and Bacteriology (Springer Verlag, Munich, 1988).
8. Brieger, L. Untersuchungen über Ptomaine Part III (Hirschwald, Berlin, 1886).
9. Koch, R. R. Koch's Vortrag über die Cholera. Fortschr. Med. 16, 121-135 (1884).
10. Koch, R. R. Koch's Vortrag über die Cholera. Fortschr. Med. 17, 141-169 (1684).
11. Pfeiffer, R. Weitere Untersuchungen über das Wesen der Choleraimmunität und über spezifisch bacterizide Prozesse. Z. Hyg. 18, 1-16 (1894).
12. Pfeiffer, R. Untersuchungen über das Choleragift. Z. Hyg. 11, 393-411 (1892).
13. Wolff, A. Über Grundgesetze der Immunität. Zentralbl. Bakteriol. 37, 390-397 (1904).
14. Rietschel, E. Th. & Cavaillon, J.-M. Endotoxin and anti-endotoxin. The contribution of the schools of Koch and Pasteur: life, milestone-experiments and concepts of Richard Pfeiffer (Berlin) and Alexandre Besredka (Paris). Historical perspective. J. Endotoxin Res. 8, 3-16; 71-82 (2002).
15. Rietschel, E. Th. & Westphal, O. in Endotoxin in Health and Disease (eds Brade, H., Opal, S. M., Vogel, S. N. & Morrison, D. C.) 1-29 (Marcel Dekker, New York, 1999).
16. Centanni, E. Untersuchungen über das Infektionsfieber - das Fiebergift der Bakterien. Dtsch. Med. Wochenschr. 20, 148-153 (1894).
17. Coley-Nauts, H., Swift, W. E. & Coley, B. L. The treatment of malignant tumors by bacterial toxins as developed by the late William B. Coley, M. D., revised in the light of modern research. Cancer Res. 6, 205-216 (1948).
18. Shear, M. J. & Turner, F. C. Chemical treatment of tumors. V. Isolation of the hemorrhage-producing fraction from Serratia marcescens (Bacillus prodigiosus) culture filtrates. J. Natl Cancer Inst. 4, 81-97 (1943).
19. Raetz, R. H. & Whitfeld, C. Lipopolysaccharide endotoxins. Annu. Rev. Biochem. 71, 635-700 (2002).
20. Galanos, C. et al. Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities. Eur. J. Biochem. 148, 1-5 (1985).
21. Schromm, A. B. et al. The charge of endotoxin molecules influences their conformation and IL-6-inducing capacity. J. Immunol. 161, 5464-5471 (1998).
22. Ferguson, A. D., Hofmann, E., Coulton, J. W., Diederichs, K. & Welte, W. Siderophore-mediated iron transport: crystal structure of FhuA with bound lipopolysaccharide. Science 282, 2215-2220 (1996).
23. Mühlradt, P. F., Kiess, M., Meyer, H., Süssmuth, R. & Jung, G. Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at picomolar concentration. J. Exp. Med. 185, 1951-1958 (1997).
24. Weidemann, B. et al. Specific binding of soluble peptidoglycan and muramyldipeptide to CD14 on human monocytes. Infect. Immun. 65, 858-864 (1997).
25. Morath, S., Geyer, A. & Hartung, T. Structure-function relationship of cytokine induction by lipoteichoic acid from Staphylococcus aureus. J. Exp. Med. 193, 393-398 (2001).
26. Wagner, H. Interactions between bacterial CpG-DNA and TLR9 bridge innate and adaptive immunity. Curr. Opin. Microbiol. 5, 62-69 (2002).
27. Heppner, G. & Weiss, D. W. High susceptibility of strain A mice to endotoxin and endotoxin-red blood cell mixtures. J. Bacteriol. 90, 696-703 (1965).
28. Watson, J. & Riblet, R. Genetic control of responses to bacterial lipopolysaccharides in mice. I. Evidence for a single gene that influences mitogenic and immunogenic respones to lipopolysaccharides. J. Exp. Med. 140, 1147-1161 (1974).
29. Watson, J. & Riblet, R. Genetic control of responses to bacterial lipopolysaccharides in mice. II. A gene that influences a membrane component involved in the activation of bone marrow-derived lymphocytes by lipopolysaccharides. J. Immunol. 114, 1462-1468 (1975).
30. Coutinho, A., Forni, L., Melchers, F. & Watanabe, T. Genetic defect in responsiveness to the B-cell mitogen lipopolysaccharide. Eur. J. Immunol. 7, 325-328 (1977).
31. Coutinho, A., Forni, L. & Watanabe, T. Genetic and functional characterization of an antiserum to the lipid A- specific triggering receptor on murine B lymphocytes. Eur. J. Immunol. 8, 63-67 (1978).
32. Moore, R. N., Goodrum, K. J. & Berry, L. J. Mediation of an endotoxic effect by macrophages. J. Reticuloendothel. Soc. 19, 187-197 (1976).
33. Michalek, S. M., Moore, R. N., McGhee, J. R., Rosenstreich, D. L. & Mergenhagen, S. E. The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxin. J. Infect. Dis. 141, 55-63 (1980).
34. Finkelstein, R. A. Observations on mode of action of endotoxin in chick embryos. Proc. Soc. Exp. Biol. Med. 115, 702-707 (1964).
35. Berczi, I., Bertok, L. & Bereznai, T. Comparative studies on the toxicity of Escherichia coli lipopolysaccharide endotoxin in various animal species. Can. J. Microbiol. 12, 1070-1071 (1966).
36. Berger, F. M. The effect of endotoxin on resistance to infection and disease. Adv. Pharmacol. 5, 19-46 (1967).
37. Neter, E. Endotoxins and the immune response. Curr. Top. Microbiol. Immunol. 47, 82-124 (1969).
38. O'Brien, A. D. et al. Genetic control of susceptibility to Salmonella typhimurium in mice: role of the LPS gene. J. Immunol. 124, 20-24 (1980).
39. Rosenstreich, D. L., Weinblatt, A. C. & O'Brien, A. D. Genetic control of resistance to infection in mice. CRC Crit. Rev. Immunol. 3, 263-330 (1982).
40. Hagberg, L. et al. Difference in susceptibility to Gram-negative urinary tract infection between C3H/HeJ and C3H/HeN mice. Infect. Immun. 46, 839-844 (1984).
41. Woods, J. P., Frelinger, J. A., Warrack, G. & Cannon, J. G. Mouse genetic locus Lps influences susceptibility to Neisseria meningitidis infection. Infect. Immun. 56, 1950-1955 (1988).
42. d mice. FEMS Immunol. Med. Microbiol. 13, 235-238 (1996).
43. Mitchell, C. R., Kempton, J. B., Scott-Tyler, B. & Trune, D. R. Otitis media incidence and impact on the auditory brain stem response in lipopolysaccharide-nonresponsive C3H/HeJ mice. Otolaryngol. Head Neck Surg. 117, 459-464 (1997).
44. Beutler, B. et al. Identity of tumour-necrosis factor and the macrophage-secreted factor cachectin. Nature 316, 552-554 (1985).
45. Beutler, B., Milsark, I. W. & Cerami, A. Passive immunization against cachectin/tumor necrosis factor (TNF) protects mice from the lethal effect of endotoxin. Science 229, 869-871 (1985).
46. Havell, E. A. Production of tumor necrosis factor during murine listeriosis. J. Immunol. 139, 4225-4231 (1987).
47. Kindler, V., Sappino, A.-P., Grau, G. E., Piguet, P.-F. & Vassalli, P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell 56, 731-740 (1989).
48. Blanchard, D. K., Djeu, J. Y., Klein, T. W., Friedman, H. & Stewart, W. E. II. Protective effects of tumor necrosis factor in experimental Legionella pneumophila infections of mice via activation of PMN function. J. Leukocyte Biol. 43, 429-435 (1988).
49. Cross, A. S., Sadoff, J. C., Kelly, N., Bernton, E. & Gemski, P. Pretreatment with recombinant murine tumor necrosis factor-α/cachectin and murine interleukin-1α protects mice from lethal bacterial infection. J. Exp. Med. 169, 2021-2027 (1989).
50. Desiderio, J. V., Kiener, P. A., Lin, P. F. & Warr, G. A. Protection of mice against Listeria monocytogenes infection by recombinant human tumor necrosis factor-α. Infect. Immun. 57, 1615-1617 (1989).
51. Sultzer, B. M. Genetic control of leucocyte responses to endotoxin. Nature 219, 1253-1254 (1968).
52. Butler, L. D. et al. Interleukin-1-induced pathophysiology: induction of cytokines, development of histopathologic changes, and immunopharmacologic intervention. Clin. Immunol. Immunopathol. 53, 400-421 (1989).
53. Car, B. D. et al. Interferon-γ receptor-deficient mice are resistant to endotoxic shock. J. Exp. Med. 179, 1437-1444 (1994).
54. Tobias, P. S., Soldau, K. & Ulevitch, R. J. Isolation of a lipopolysaccharide-binding acute phase reactant from rabbit serum. J. Exp. Med. 164, 777-793 (1986).
55. Tobias, P. S., Mathison, J. C. & Ulevitch, R. J. A family of lipopolysaccharide binding proteins involved in responses to Gram-negative sepsis. J. Biol. Chem. 263, 13479-13481 (1988).
56. Wright, S. D., Tobias, P. S., Ulevitch, R. J. & Ramos, R. A. Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particles for recognition by a novel receptor on macrophages. J. Exp. Med. 170, 1231-1241 (1989).
57. Schumann, R. R. et al. Structure and function of lipopolysaccharide binding protein. Science 249, 1429-1431 (1990).
58. Wright, S. D., Ramos, R. A., Tobias, P. S., Ulevitch, R. J. & Mathison, J. C. CD14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249, 1431-1433 (1990).
59. Shakhov, A. N., Collart, M. A., Vassalli, P., Nedospasov, S. A. & Jongeneel, C. V. κB-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor-α gene in primary macrophages. J. Exp. Med. 171, 35-47 (1990).
60. Han, J., Lee, J. D., Bibbs, L. & Ulevitch, R. J. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science 265, 808-811 (1994).
61. Hambleton, J., Weinstein, S. L., Lem, L. & DeFranco, A. L. Activation of c-Jun N-terminal kinase in bacterial lipopolysaccharide-stimulated macrophages. Proc. Natl Acad. Sci. USA 93, 2774-2778 (1996).
62. Herrera-Velit, P. & Reiner, N. E. Bacterial lipopolysaccharide induces the association and coordinate activation of p53/56lyn and phosphatidylinositol 3-kinase in human monocytes. J. Immunol. 156, 1157-1165 (1996).
63. Herrera-Velit, P., Knutson, K. L. & Reiner, N. E. Phosphatidylinositol 3-kinase-dependent activation of protein kinase Cζ in bacterial lipopolysaccharide-treated human monocytes. J. Biol. Chem. 212, 16445-16452 (1997).
64. Poltorak, A. et al. Genetic and physical mapping of the Lps locus - identification of the toll-4 receptor as a candidate gene in the critical region. Blood Cells Mol. Dis. 24, 340-355 (1998).
65. Poltorak, A. et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282, 2085-2088 (1998).
66. Anderson, K. V., Bokla, L. & Nusslein-Volhard, C. Establishment of dorsal-ventral polarity in the Drosophila embryo: the induction of polarity by the Toll gene product. Cell 42, 791-798 (1985).
67. Lemeitre, B., Nicolas, E., Michaut, L., Reichhart, J. M. & Hoffmann, J. A. The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86, 973-983 (1996).
68. Reichhart, J. M. et al. Insect immunity: developmental and inducible activity of the Drosophila diptericin promoter. EMBO J. 11, 1469-1477 (1992).
69. Engstrom, Y. et al. κB-like motifs regulate the induction of immune genes in Drosophila. J. Mol. Biol. 232, 327-333 (1993).
70. Gay, N. J. & Keith, F. J. Drosophila Toll and IL-1 receptor. Nature 351, 355-356 (1991).
71. Nomura, N. et al. Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1. DNA Res. 1, 27-35 (1994).
72. Taguchi, T., Mitcham, J. L., Dower, S. K., Sims, J. E. & Testa, J. R. Chromosomal localization of TIL, a gene encoding a protein related to the Drosophila transmembrane receptor Toll, to human chromosome 4p14. Genomics 32, 486-488 (1996).
73. Medzhitov, R., Preston-Hudburt, P. & Janeway, C. A. Jr. A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388, 394-397 (1997).
74. Mansell, A., Reinicke, A., Worrall, D. M. & O'Neill, L. A. The serine protease inhibitor antithrombin III inhibits LPS-mediated NF-κB activation by TLR-4. FEBS Lett. 508, 313-317 (2001).
75. Poltorak, A., Ricciardi-Castagnoli, P., Citterio, A. & Beutler, B. Physical contact between LPS and Tlr4 revealed by genetic complementation. Proc. Natl Acad. Sci. USA 97, 2163-2167 (2000).
76. Lien, E. et al. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J. Clin. Invest. 105, 497-504 (2000).
77. da Silva, C. J., Soldau, K., Christen, U., Tobias, P. S. & Ulevitch, R. J. 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. 278, 21129-21135 (2001).
78. Rock, F. L., Hardiman, G., Timans, J. C., Kastelein, R. A. & Bazan, J. F. A family of human receptors structurally related to Drosophila Toll. Proc. Natl Acad. Sci. USA 95, 588-593 (1998).
79. Chaudhary, P. M. et al. Cloning and characterization of two Toll/interleukin-1 receptor-like genes TIL3 and TIL4: evidence for a multi-gene receptor family in humans. Blood 91, 4020-4027 (1998).
80. Takeuchi, O. et al. TLR6: a novel member of an expanding Toll-like receptor family. Gene 231, 59-65 (1999).
81. Du, X., Poltorak, A., Wei, Y. & Beutler, B. Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur. Cytokine Netw. 11, 362-371 (2000).
82. Chuang, T. H. & Ulevitch, R. J. Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9. Eur. Cytokine Netw. 11, 372-378 (2000).
83. Chuang, T. & Ulevitch, R. J. Identification of hTLR10: a novel human Toll-like receptor preferentially expressed in immune cells. Biochim. Biophys. Acta 1518, 157-161 (2001).
84. Takeuchi, O. et al. Differential roles of TLR2 and TLR4 in recognition of Gram-negative and Gram-positive bacterial cell wall components. Immunity 11, 443-451 (1999).
85. Takeuchi, O. et al. Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int. Immunol. 13, 933-940 (2001).
86. Hemmi, H. et al. A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745 (2000).
87. Kawai, T., Adachi, O., Ogawa, T., Takeda, K. & Akira, S. Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity 11, 115-122 (1999).
88. Hemmi, H. et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nature Immunol. 3, 196-200 (2002).
89. Adachi, O. et al. Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity 9, 143-150 (1998).
90. Ozinsky, A. et al. The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc. Natl Acad. Sci. USA 97, 13766-13771 (2000).
91. Takeuchi, O. et al. Cutting edge: role of Toll-like receptor 1 in mediating immune response to microbial lipoproteins. J. Immunol. 169, 10-14 (2002).
92. Hayashi, F. et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099-1103 (2001).
93. Alexopoulou, L., Holt, A. C., Medzhitov, R. & Flavell, R. A. Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3. Nature 413, 732-738 (2001).
94. Hemmi, H. et al. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Nature Immunol. 3, 196-200 (2002).
95. Ahmad-Nejad, P. et al. Bacterial CpG-DNA and lipopolysaccharides activate Toll-like receptors at distinct cellular compartments. Eur. J. Immunol. 32, 1958-1968 (2002).
96. Shimazu, R. et al. MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J. Exp. Med. 189, 1777-1782 (1999).
97. Nagai, Y. et al. Essential role of MD-2 in LPS responsiveness and TLR4 distribution. Nature Immunol. 3, 667-672 (2002).
98. Schromm, A. B. et al. Molecular genetic analysis of an endotoxin nonresponder mutant cell line: a point mutation in a conserved region of MD-2 abolishes endotoxin-induced signalling. J. Exp. Med. 194, 79-88 (2001).