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
  • [31] DROSOPHILA TOLL AND IL-1 RECEPTOR
    GAY, NJ
    KEITH, FJ
    [J]. NATURE, 1991, 351 (6325) : 355 - 356
  • [32] MAPKK-independent activation of p38α mediated by TAB1-dependent autophosphorylation of p38α
    Ge, BX
    Gram, H
    Di Padova, F
    Huang, B
    New, L
    Ulevitch, RJ
    Luo, Y
    Han, JH
    [J]. SCIENCE, 2002, 295 (5558) : 1291 - 1294
  • [33] INSECT IMMUNITY - THE DIPTERICIN PROMOTER CONTAINS MULTIPLE FUNCTIONAL REGULATORY SEQUENCES HOMOLOGOUS TO MAMMALIAN ACUTE-PHASE RESPONSE ELEMENTS
    GEORGEL, P
    MEISTER, M
    KAPPLER, C
    LEMAITRE, B
    REICHHART, JM
    HOFFMANN, JA
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 197 (02) : 508 - 517
  • [34] GEPPERT TD, 1994, MOL MED, V1, P93
  • [35] GRATIA A, 1931, C R SOC BIOL, V108, P421
  • [36] CHARACTERIZATION OF MACROPHAGE FUNCTION IN "MYCOBACTERIUM-LEPRAEMURIUM-INFECTED MICE - SENSITIVITY OF MICE TO ENDOTOXIN AND RELEASE OF MEDIATORS AND LYSOSOMAL-ENZYMES AFTER ENDOTOXIN TREATMENT
    HA, DKK
    GARDNER, ID
    LAWTON, JWM
    [J]. PARASITE IMMUNOLOGY, 1983, 5 (05) : 513 - 526
  • [37] Regulation of macrophage gene expression by pro- and anti-inflammatory cytokines
    Hamilton, TA
    Ohmori, Y
    Tebo, JM
    Kishore, R
    [J]. PATHOBIOLOGY, 1999, 67 (5-6) : 241 - 244
  • [38] A MAP KINASE TARGETED BY ENDOTOXIN AND HYPEROSMOLARITY IN MAMMALIAN-CELLS
    HAN, J
    LEE, JD
    BIBBS, L
    ULEVITCH, RJ
    [J]. SCIENCE, 1994, 265 (5173) : 808 - 811
  • [39] ENDOTOXIN-RESPONSIVE SEQUENCES CONTROL CACHECTIN TUMOR NECROSIS FACTOR BIOSYNTHESIS AT THE TRANSLATIONAL LEVEL
    HAN, J
    BROWN, T
    BEUTLER, B
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 171 (02) : 465 - 475
  • [40] The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
    Hayashi, F
    Smith, KD
    Ozinsky, A
    Hawn, TR
    Yi, EC
    Goodlett, DR
    Eng, JK
    Akira, S
    Underhill, DM
    Aderem, A
    [J]. NATURE, 2001, 410 (6832) : 1099 - 1103