Endotoxin, toll-like receptor 4, and the afferent limb of innate immunity

Current Opinion in Microbiology

Volumn 3, Issue 1, 2000, Pages 23-28

  Beutler, Bruce ^a  

^a UNIVERSITY OF TEXAS AT DALLAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIUM LIPOPOLYSACCHARIDE; CELL RECEPTOR; ENDOTOXIN; TOLL LIKE RECEPTOR 4; UNCLASSIFIED DRUG;

BACTERIAL IMMUNITY; DNA POLYMORPHISM; GRAM NEGATIVE INFECTION; MOLECULAR CLONING; MOLECULAR RECOGNITION; NONHUMAN; PROTEIN DEGRADATION; PROTEIN FAMILY; REVIEW; SEQUENCE ANALYSIS; SIGNAL TRANSDUCTION; SPECIES DIFFERENCE;

BACTERIA (MICROORGANISMS); NEGIBACTERIA; VERTEBRATA;

EID: 0033968116     PISSN: 13695274     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1369-5274(99)00046-6     Document Type: Review

References (48)

1. Nobel Lectures on World Wide Web URL: http://www.nobel.se/laureates/medicine-1908-press.html.
2. Rietschel E.T., Westphal O. Endotoxin: historical perspectives. Brade H., Opal S.M., Vogel S.N., Morrison D.C. Endotoxin Health and Disease. 1999;1-30 Marcel Dekker, Inc, Basel.
3. Berczi I., Bertok L., Bereznai T. Comparative studies on the toxicity of Escherichia coli lipopolysaccharide endotoxin in various animal species. Can J Microbiol. 12:1966;1070-1071.
4. Finkelstein R.A. Observations on mode of action of endotoxin in chick embryos. Proc Soc Exp Biol Med. 115:1964;702-707.
5. Redl H., Bahrami S., Schlag G., Traber D.L. Clinical detection of LPS and animal models of endotoxemia. Immunobiology. 187:1993;330-345.
6. 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. 141:1980;55-63.
7. Beutler B., Milsark I.W., Cerami A. Passive immunization against cachectin/tumor necrosis factor (TNF) protects mice from the lethal effect of endotoxin. Science. 229:1985;869-871.
8. Freudenberg M.A., Keppler D., Galanos C. Requirement for lipopolysaccharide-responsive macrophages in galactosamine-induced sensitization to endotoxin. Infect Immun. 51:1986;891-895.
9. 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. 249:1990;1431-1433.
10. 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. 263:1988;13479-13481.
11. Tobias P.S., Soldau K., Ulevitch R.J. Identification of a lipid A binding site in the acute phase reactant lipopolycaccharide binding protein. J Biol Chem. 264:1989;10867-10871.
12. Wright S.D., Tobias P.S., Ulevitch R.J., Ramos R.A. Lipopolysaccharide (LPS) binding protein opsonizes LPS-bearing particle for recognition by a novel receptor on macrophages. J Exp Med. 170:1989;1231-1241.
13. Tobias P.S., Soldau K., Gegner J.A., Mintz D., Ulevitch R.J. Lipopolysaccharide binding protein-mediated complexation of lipopolysaccharide with soluble CD14. J Biol Chem. 270:1995;10482-10488.
14. Yu B., Wright S.D. Catalytic properties of lipopolysaccharide (LPS) binding protein - transfer of LPS to soluble CD14. J Biol Chem. 271:1996;4100-4105.
15. Yu B., Hailman E., Wright S.D. Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids. J Clin Invest. 99:1997;315-324.
16. Sultzer B.M. Genetic control of leucocyte responses to endotoxin. Nature. 219:1968;1253-1254.
17. Watson J., Riblet R., Taylor B.A. The response of recombinant inbred strains of mice to bacterial lipopolysaccharides. J Immunol. 118:1977;2088-2093.
18. Watson J., Kelly K., Largen M., Taylor B.A. The genetic mapping of a defective LPS response gene in C3H/HeJ mice. J Immunol. 120:1978;422-424.
19. Coutinho A., Forni L., Melchers F., Watanabe T. Genetic defect in responsiveness to the B cell mitogen lipopolysaccharide. Eur J Immunol. 7:1977;325-328.
20. Coutinho A., Meo T. Genetic basis for unresponsiveness to lipopolysaccharide in C57BL/10Cr mice. Immunogenetics. 7:1978;17-24.
21. O'Brien A.D., Rosenstreich D.L., Scher I., Campbell G.H., MacDermott R.P., Formal S.B. Genetic control of susceptibility to Salmonella typhimurium in mice: role of the LPS gene. J Immunol. 124:1980;20-24.
22. Rosenstreich D.L., Weinblatt A.C., O'Brien A.D. Genetic control of resistance to infection in mice. CRC Crit Rev Immunol. 3:1982;263-330.
23. Lemaitre 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. 86:1996;973-983.
24. Levashina E.A., Langley E., Green C., Gubb D., Ashburner M., Hoffmann J.A., Reichhart J.M. Constitutive activation of toll-mediated antifungal defense in serpin-deficient Drosophila. Science. 285:1999;1917-1919. This paper demonstrates that Spätzle, the ligand for Drosophila Toll, is generated by a proteolytic cascade during infection, and at that, by a cascade distinct from the cascade which is activated during developmental polarization of the embryo.
25. Williams M.J., Rodriguez A., Kimbrell D.A., Eldon E.D. The 18-wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense. EMBO J. 16:1997;6120-6130.
26. Gay N.J., Keith F.J. Drosophila Toll and IL-1 receptor [letter]. Nature. 351:1991;355-356.
27. Heguy A., Baldari C.T., Macchia G., Telford J.L., Melli M. Amino acids conserved in interleukin-1 receptors (IL-1Rs) and the Drosophila toll protein are essential for IL-1R signal transduction. J Biol Chem. 267:1992;2605-2609.
28. Kuhns D.B., Long P.D., Gallin J.I. Endotoxin and IL-1 hyporesponsiveness in a patient with recurrent bacterial infections. J Immunol. 158:1997;3959-3964.
29. Poltorak A., Smirnova I., He X.L., Liu M.Y., Van Huffel C., McNally O., Birdwell D., Alejos E., Silva M., Du X.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. 24:1998;340-355. High density genetic mapping and sequencing revealed that Tlr4 was the sole gene in the Lps critical region, and hence, implicated it as the probable substratum of LPS signal transduction.
30. Medzhitov R., Preston-Hurlburt P., Janeway C.A. Jr. A human homologue of the Drosophila, Toll, protein signals activation of adaptive immunity. Nature. 388:1997;394-397.
31. Poltorak A., He X., Smirnova I., Liu M-Y., Van Huffel C., Du X., Birdwell D., Alejos E., Silva M., Galanos C.et al. Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 282:1998;2085-2088. Formal proof of the identity of Lps and Tlr4 was provided by the demonstration of allelic Tlr4 defects in two LPS-resistant strains of mice.
32. Hoshino K., Takeuchi O., Kawai T., Sanjo H., Ogawa T., Takeda Y., Takeda K., Akira S. Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol. 162:1999;3749-3752. Targeted deletion of the mouse Tlr4 locus produced a phenocopy of the natural deletion mutation observed in C57BL/10ScCr mice.
33. Yang R-B., Mark M.R., Gray A., Huang A., Xie M.H., Zhang M., Goddard A., Wood W.I., Gurney A.L., Godowski P.J. Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature. 395:1998;284-288.
34. Kirschning C.J., Wesche H., Merrill A.T., Rothe M. Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. J Exp Med. 188:1998;2091-2097.
35. 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. Immunity. 11:1999;443-451. Targeted deletion of the mouse Tlr2 locus is compatible with normal LPS signal transduction, affirming that Tlr2 makes no contribution to LPS signaling. However, Tlr2 deficient mice show hyporesponsiveness to muramyl dipeptide, the basic constituent of bacterial peptidoglycan.
36. Heine H., Kirschning C.J., Lien E., Monks B.G., Rothe M., Golenbock D.T. Cutting edge: cells that carry a null allele for toll-like receptor 2 are capable of responding to endotoxin. J Immunol. 162:1999;6971-6975.
37. Du X., Poltorak A., Silva M., Beutter B. Analysis of Tlr4-mediated LPS signal transduction in macrophages by mutational modification of the receptor. Blood Cells Mol Dis. 25:1999;328-338.
38. Munford R.S., Hall C.L. Detoxification of bacterial lipopolysaccharides (endotoxins) by a human neutrophil enzyme. Science. 234:1986;203-205.
39. Kanegasaki S., Kojima Y., Matsuura M., Homma J.Y., Yamamoto A., Kumazawa Y., Tanamoto K., Yasuda T., Tsumita T., Imoto M. Biological activities of analogues of lipid A based chemically on the revised structural model. Comparison of mediator-inducing, immunomodulating and endotoxic activities. Eur J Biochem. 143:1984;237-242.
40. Galanos C., Lehmann V., Luderitz O., Rietschel E.T., Westphal O., Brade H., Brade L., Freudenberg M.A., Hansen-Hagge T., Luderitz T. Endotoxic properties of chemically synthesized lipid A part structures. Comparison of synthetic lipid A precursor and synthetic analogues with biosynthetic lipid A precursor and free lipid A. Eur J Biochem. 140:1984;221-227.
41. Birkland T.P., Cornwell R.D., Golenbock D.T., Proctor R.A. Comparative study of lipopolysaccharide-, lipid IVa-, and lipid X-induced tumor necrosis factor production in murine macrophage-like cell lines. Adv Exp Med Biol. 256:1990;399-402.
42. Dal Nogare A.R., Yarbrough W.C. Jr. A comparison of the effects of intact and deacylated lipopolysaccharide on human polymorphonuclear leukocytes. J Immunol. 144:1990;1404-1410.
43. Golenbock D.T., Hampton R.Y., Qureshi N., Takayama K., Raetz C.R. Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes. J Biol Chem. 266:1991;19490-19498.
44. Pohlman T.H., Munford R.S., Harlan J.M. Deacylated lipopolysaccharide inhibits neutrophil adherence to endothelium induced by lipopolysaccharide in vitro. J Exp Med. 165:1987;1393-1402.
45. Loppnow H., Brade H., Durrbaum I., Dinarello C.A., Kusumoto S., Rietschel E.T., Flad H.D. IL-1 induction-capacity of defined lipopolysaccharide partial structures. J Immunol. 142:1989;3229-3238.
46. Wang M.H., Flad H.D., Feist W., Brade H., Kusumoto S., Rietschel E.T., Ulmer A.J. Inhibition of endotoxin-induced interleukin-6 production by synthetic lipid A partial structures in human peripheral blood mononuclear cells. Infect Immunol. 59:1991;4655-4664.
47. Delude R.L., Savedra R., Zhao H.L., Thieringer R., Yamamoto S., Fenton M.J., Golenbock D.T. CD14 enhances cellular responses to endotoxin without imparting ligand-specific recognition. Proc Natl Acad Sci USA. 92:1995;9288-9292.
48. Poltorak A., Ricciardi-Castagnoli P., Citterio A., Beutler B. Physical contact between LPS and Tlr4 revealed by genetic complementation. Proc Natl Acad Sci USA. 2000;. in press. This paper uses a genetic complementation strategy. Direct interaction between Tlr4 and lipid A (the toxic center of LPS) is documented, in that it is proven that Tlr4 directly interprets lipid A structure.