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
  • [1] Cutting edge: Cell surface expression and lipopolysaccharide signaling via the Toll-like receptor 4-MD-2 complex on mouse peritoneal macrophages
    Akashi, S
    Shimazu, R
    Ogata, H
    Nagai, Y
    Takeda, K
    Kimoto, M
    Miyake, K
    [J]. JOURNAL OF IMMUNOLOGY, 2000, 164 (07) : 3471 - 3475
  • [2] Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
    Alexopoulou, L
    Holt, AC
    Medzhitov, R
    Flavell, RA
    [J]. NATURE, 2001, 413 (6857) : 732 - 738
  • [3] TLR4 mutations are associated with endotoxin hyporesponsiveness in humans
    Arbour, NC
    Lorenz, E
    Schutte, BC
    Zabner, J
    Kline, JN
    Jones, M
    Frees, K
    Watt, JL
    Schwartz, DA
    [J]. NATURE GENETICS, 2000, 25 (02) : 187 - +
  • [4] COMPARATIVE STUDIES ON TOXICITY OF ESCHERICHIA COLI LIPOPOLYSACCHARIDE ENDOTOXIN IN VARIOUS ANIMAL SPECIES
    BERCZI, I
    BERTOK, L
    BEREZNAI, T
    [J]. CANADIAN JOURNAL OF MICROBIOLOGY, 1966, 12 (05) : 1070 - +
  • [5] SOME METABOLIC ASPECTS OF TOLERANCE TO BACTERIAL ENDOTOXIN
    BERRY, LJ
    SMYTHE, DS
    [J]. JOURNAL OF BACTERIOLOGY, 1965, 90 (04) : 970 - &
  • [6] PURIFICATION OF CACHECTIN, A LIPOPROTEIN-LIPASE SUPPRESSING HORMONE SECRETED BY ENDOTOXIN-INDUCED RAW 264.7 CELLS
    BEUTLER, B
    MAHONEY, J
    LETRANG, N
    PEKALA, P
    CERAMI, A
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1985, 161 (05) : 984 - 995
  • [7] Toll-like receptors: how they work and what they do
    Beutler, B
    [J]. CURRENT OPINION IN HEMATOLOGY, 2002, 9 (01) : 2 - 10
  • [8] IDENTITY OF TUMOR NECROSIS FACTOR AND THE MACROPHAGE-SECRETED FACTOR CACHECTIN
    BEUTLER, B
    GREENWALD, D
    HULMES, JD
    CHANG, M
    PAN, YCE
    MATHISON, J
    ULEVITCH, R
    CERAMI, A
    [J]. NATURE, 1985, 316 (6028) : 552 - 554
  • [9] PASSIVE-IMMUNIZATION AGAINST CACHECTIN TUMOR NECROSIS FACTOR PROTECTS MICE FROM LETHAL EFFECT OF ENDOTOXIN
    BEUTLER, B
    MILSARK, IW
    CERAMI, AC
    [J]. SCIENCE, 1985, 229 (4716) : 869 - 871
  • [10] BOIVIN A, 1946, Schweiz Z Pathol Bakteriol, V9, P505