Report

Host Defense Mechanisms Triggered by Microbial Lipoproteins Through Toll-Like Receptors

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Science  30 Jul 1999:
Vol. 285, Issue 5428, pp. 732-736
DOI: 10.1126/science.285.5428.732

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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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed. E-mail: rmodlin{at}mednet.ucla.edu

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