The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
Fumitaka Hayashi,
Kelly D. Smith,
Adrian Ozinsky,
Thomas R. Hawn,
Eugene C. Yi,
David R. Goodlett,
Jimmy K. Eng,
Shizuo Akira,
David M. Underhill and
Alan Aderem ()
Additional contact information
Fumitaka Hayashi: Department of Immunology
Kelly D. Smith: Department of Pathology
Adrian Ozinsky: Institute for Systems Biology
Thomas R. Hawn: University of Washington
Eugene C. Yi: Institute for Systems Biology
David R. Goodlett: Institute for Systems Biology
Jimmy K. Eng: Institute for Systems Biology
Shizuo Akira: Research Institute for Microbial Diseases, Osaka University
David M. Underhill: Institute for Systems Biology
Alan Aderem: Institute for Systems Biology
Nature, 2001, vol. 410, issue 6832, 1099-1103
Abstract:
Abstract The innate immune system recognizes pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, but not on the host. Toll-like receptors (TLRs) recognize PAMPs and mediate the production of cytokines necessary for the development of effective immunity1,2,3,4. Flagellin, a principal component of bacterial flagella, is a virulence factor that is recognized by the innate immune system in organisms as diverse as flies, plants and mammals5,6,7,8,9,10,11. Here we report that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-κB and stimulates tumour necrosis factor-α production. TLR5-stimulating activity was purified from Listeria monocytogenes culture supernatants and identified as flagellin by tandem mass spectrometry. Expression of L. monocytogenes flagellin in non-flagellated Escherichia coli conferred on the bacterium the ability to activate TLR5, whereas deletion of the flagellin genes from Salmonella typhimurium abrogated TLR5-stimulating activity. All known TLRs signal through the adaptor protein MyD88. Mice challenged with bacterial flagellin rapidly produced systemic interleukin-6, whereas MyD88-null mice did not respond to flagellin. Our data suggest that TLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flagellated bacterial pathogens.
Date: 2001
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DOI: 10.1038/35074106
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