The innate immune response to bacterial flagellin is mediated by Toll-likereceptor 5

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 cytokin es necessary for the development of effective immunity(1-4). Flagellin, a p rincipal component of bacterial flagella, is a virulence factor that is rec ognized by the innate immune system in organisms as diverse as flies, plant s and mammals(5-11). Here we report that mammalian TLR5 recognizes bacteria l flagellin from both Gram-positive and Gram-negative bacteria, and that ac tivation of the receptor mobilizes the nuclear factor NF-kappaB and stimula tes 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 flag ellin in non-flagellated Escherichia coli conferred on the bacterium the ab ility to activate TLR5, whereas deletion of the flagellin genes from Salmon ella typhimurium abrogated TLR5-stimulating activity. All known TLRs signal through the adaptor protein MyD88. Mice challenged with bacterial flagelli n rapidly produced systemic interleukin-6, whereas MyD88-null mice did not respond to flagellin. Our data suggest that TLR5, a member of the evolution arily conserved Toll-like receptor family, has evolved to permit mammals sp ecifically to detect flagellated bacterial pathogens.