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

HD Brightbill, DH Libraty, SR Krutzik, RB Yang… - Science, 1999 - science.org
HD Brightbill, DH Libraty, SR Krutzik, RB Yang, JT Belisle, JR Bleharski, M Maitland…
Science, 1999science.org
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 …
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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