Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors.
The generation of cell-mediated immunity against many infectious pathogens involves the production of interleukin-12 (IL-12), a key signal of the innate immune system. Yet, for many pathogens, the molecules that induce IL-12 production by macrophages and the mechanisms by which they do so remain undefined. Here it is shown that microbial lipoproteins are potent stimulators of IL-12 production by human macrophages, and that induction is mediated by Toll-like receptors (TLRs). Several lipoproteins stimulated TLR-dependent transcription of inducible nitric oxide synthase and the production of nitric oxide, a powerful microbicidal pathway. Activation of TLRs by microbial lipoproteins may initiate innate defense mechanisms against infectious pathogens.
Brightbill
H D
HD
Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California Los Angeles School of Medicine, Los Anges, CA 90095, USA.
Libraty
D H
DH
Krutzik
S R
SR
Yang
R B
RB
Belisle
J T
JT
Bleharski
J R
JR
Maitland
M
M
Norgard
M V
MV
Plevy
S E
SE
Smale
S T
ST
Brennan
P J
PJ
Bloom
B R
BR
Godowski
P J
PJ
Modlin
R L
RL
D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics; D008070:Lipopolysaccharides / Q000276:immunology; D008074:Lipoproteins / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016328:NF-kappa B / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D051193:Toll-Like Receptors; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
C075966:Ag38 antigen, Mycobacterium tuberculosis; D000942:Antigens, Bacterial; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D018664:Interleukin-12; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse