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

Hans D. Brightbill; Daniel H. Libraty; Stephan R. Krutzik; Ruey Bing Yang; John T. Belisle; Joshua R. Bleharski; Michael Maitland; Michael V. Norgard; Scott E. Plevy; Stephen T. Smale; Patrick J. Brennan; Barry R. Bloom; Paul J. Godowski; Robert L. Modlin

doi:10.1126/science.285.5428.732

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

Hans D. Brightbill, Daniel H. Libraty, Stephan R. Krutzik, Ruey Bing Yang, John T. Belisle, Joshua R. Bleharski, Michael Maitland, Michael V. Norgard, Scott E. Plevy, Stephen T. Smale, Patrick J. Brennan, Barry R. Bloom, Paul J. Godowski, Robert L. Modlin

Research output: Contribution to journal › Article › peer-review

1356 Scopus citations

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.

Original language	English (US)
Pages (from-to)	732-736
Number of pages	5
Journal	Science
Volume	285
Issue number	5428
DOIs	https://doi.org/10.1126/science.285.5428.732
State	Published - Jul 30 1999

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10.1126/science.285.5428.732

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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. (1999). Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science, 285(5428), 732-736. https://doi.org/10.1126/science.285.5428.732

Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. / Brightbill, Hans D.; Libraty, Daniel H.; Krutzik, Stephan R.; Yang, Ruey Bing; Belisle, John T.; Bleharski, Joshua R.; Maitland, Michael; Norgard, Michael V.; Plevy, Scott E.; Smale, Stephen T.; Brennan, Patrick J.; Bloom, Barry R.; Godowski, Paul J.; Modlin, Robert L.

In: Science, Vol. 285, No. 5428, 30.07.1999, p. 732-736.

Research output: Contribution to journal › Article › peer-review

Brightbill, Hans D. ; Libraty, Daniel H. ; Krutzik, Stephan R. ; Yang, Ruey Bing ; Belisle, John T. ; Bleharski, Joshua R. ; Maitland, Michael ; Norgard, Michael V. ; Plevy, Scott E. ; Smale, Stephen T. ; Brennan, Patrick J. ; Bloom, Barry R. ; Godowski, Paul J. ; Modlin, Robert L. / Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. In: Science. 1999 ; Vol. 285, No. 5428. pp. 732-736.

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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.",

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AU - Bleharski, Joshua R.

AU - Maitland, Michael

AU - Norgard, Michael V.

AU - Plevy, Scott E.

AU - Smale, Stephen T.

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

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