Innate immune responses to microbial poisons: Discovery and function of the toll-like receptors

被引:67
作者
Beutler, B [1 ]
机构
[1] Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA
关键词
LPS; lipopolysaccharide; TNF; toll-like receptors; TLR4; innate immunity;
D O I
10.1146/annurev.pharmtox.43.100901.135729
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
There are many circumstances under which a toxin exploits an endogenous receptor or another protein of host origin to work its untoward effects. In most instances, the receptor normally fulfills a function that has nothing to do with the toxin per se; that is, the toxin is not the "natural" ligand. The situation with endotoxin, however, is a remarkable one. The endotoxin receptor evolved to detect endotoxin. Why have mammals maintained a gene that can undermine their survival? The search for the endotoxin receptor answered this question and also revealed the essential function and biological strategy of the Toll-like receptors: principal sensors of the innate immune system.
引用
收藏
页码:609 / 628
页数:22
相关论文
共 112 条
  • [51] ENZYMATICALLY DEACYLATED LIPOPOLYSACCHARIDE (LPS) CAN ANTAGONIZE LPS AT MULTIPLE SITES IN THE LPS RECOGNITION PATHWAY
    KITCHENS, RL
    MUNFORD, RS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (17) : 9904 - 9910
  • [52] LIPOPOLYSACCHARIDE (LPS) PARTIAL STRUCTURES INHIBIT RESPONSES TO LPS IN A HUMAN MACROPHAGE CELL-LINE WITHOUT INHIBITING LPS UPTAKE BY A CD14-MEDIATED PATHWAY
    KITCHENS, RL
    ULEVITCH, RJ
    MUNFORD, RS
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1992, 176 (02) : 485 - 494
  • [53] A PROTEIN-KINASE INVOLVED IN THE REGULATION OF INFLAMMATORY CYTOKINE BIOSYNTHESIS
    LEE, JC
    LAYDON, JT
    MCDONNELL, PC
    GALLAGHER, TF
    KUMAR, S
    GREEN, D
    MCNULTY, D
    BLUMENTHAL, MJ
    HEYS, JR
    LANDVATTER, SW
    STRICKLER, JE
    MCLAUGHLIN, MM
    SIEMENS, IR
    FISHER, SM
    LIVI, GP
    WHITE, JR
    ADAMS, JL
    YOUNG, PR
    [J]. NATURE, 1994, 372 (6508) : 739 - 746
  • [54] LEIST M, 1995, AM J PATHOL, V146, P1220
  • [55] The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults
    Lemaitre, B
    Nicolas, E
    Michaut, L
    Reichhart, JM
    Hoffmann, JA
    [J]. CELL, 1996, 86 (06) : 973 - 983
  • [56] LIBBY P, 1986, AM J PATHOL, V124, P179
  • [57] Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide
    Lien, E
    Means, TK
    Heine, H
    Yoshimura, A
    Kusumoto, S
    Fukase, K
    Fenton, MJ
    Oikawa, M
    Qureshi, N
    Monks, B
    Finberg, RW
    Ingalls, RR
    Golenbock, DT
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2000, 105 (04) : 497 - 504
  • [58] LUDERITZ O, 1966, BACTERIOL REV, V30, P192
  • [59] LIPID - CHEMICAL STRUCTURE AND BIOLOGICAL-ACTIVITY
    LUDERITZ, O
    GALANOS, C
    LEHMANN, V
    NURMINEN, M
    RIETSCHE.ET
    ROSENFELDER, G
    SIMON, M
    WESTPHAL, O
    [J]. JOURNAL OF INFECTIOUS DISEASES, 1973, 128 (JUL) : S17 - S29
  • [60] ADAPTATION TO BACTERIAL LIPOPOLYSACCHARIDE CONTROLS LIPOPOLYSACCHARIDE-INDUCED TUMOR-NECROSIS-FACTOR PRODUCTION IN RABBIT MACROPHAGES
    MATHISON, JC
    VIRCA, GD
    WOLFSON, E
    TOBIAS, PS
    GLASER, K
    ULEVITCH, RJ
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1990, 85 (04) : 1108 - 1118