The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5.
Hayashi, Fumitaka *; Smith, Kelly D. +++; Ozinsky, Adrian +; Hawn, Thomas R. +[S]; Yi, Eugene C. +; Goodlett, David R. +; Eng, Jimmy K. +; Akira, Shizuo [//]; Underhill, David M. +; Aderem, Alan +
[Letter]
Nature.
410(6832):1099-1103, April 26, 2001.
(Format: HTML)
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 immunity 1-4. 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 mammals 5-11. 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-[kappa]B and stimulates tumour necrosis factor-[alpha] 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.
(C) 2001 Nature Publishing Group