Publication Date:
1999-07-31
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brightbill, H D -- Libraty, D H -- Krutzik, S R -- Yang, R B -- Belisle, J T -- Bleharski, J R -- Maitland, M -- Norgard, M V -- Plevy, S E -- Smale, S T -- Brennan, P J -- Bloom, B R -- Godowski, P J -- Modlin, R L -- New York, N.Y. -- Science. 1999 Jul 30;285(5428):732-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California Los Angeles School of Medicine, Los Anges, CA 90095, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10426995" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens, Bacterial/chemistry/*immunology/metabolism
;
Cell Line
;
*Drosophila Proteins
;
Gene Expression Regulation
;
Humans
;
Interleukin-12/*biosynthesis/genetics
;
Lipopolysaccharides/immunology
;
Lipoproteins/chemistry/*immunology/metabolism
;
Macrophages/*immunology/metabolism
;
Membrane Glycoproteins/*metabolism
;
Mice
;
Monocytes/*immunology/metabolism
;
Mycobacterium tuberculosis/*immunology
;
NF-kappa B/biosynthesis
;
Nitric Oxide Synthase/genetics
;
Nitric Oxide Synthase Type II
;
Promoter Regions, Genetic
;
Receptors, Cell Surface/*metabolism
;
Signal Transduction
;
Toll-Like Receptors
;
Transcription, Genetic
;
Transfection
;
Tumor Cells, Cultured
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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