The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5 View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-04

AUTHORS

Fumitaka Hayashi, Kelly D. Smith, Adrian Ozinsky, Thomas R. Hawn, Eugene C. Yi, David R. Goodlett, Jimmy K. Eng, Shizuo Akira, David M. Underhill, Alan Aderem

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. More... »

PAGES

1099-1103

Journal

TITLE

Nature

ISSUE

6832

VOLUME

410

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/35074106

    DOI

    http://dx.doi.org/10.1038/35074106

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1046017863

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/11323673


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