Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors

Science. 1999 Jul 30;285(5428):732-6. doi: 10.1126/science.285.5428.732.

H D Brightbill ¹, D H Libraty, S R Krutzik, R B Yang, J T Belisle, J R Bleharski, M Maitland, M V Norgard, S E Plevy, S T Smale, P J Brennan, B R Bloom, P J Godowski, R L Modlin

Affiliations

Affiliation

1 Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California Los Angeles School of Medicine, Los Anges, CA 90095, USA.

PMID: 10426995 DOI: 10.1126/science.285.5428.732

Abstract

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.

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