The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
- PMID: 11323673
- DOI: 10.1038/35074106
The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
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 immunity. 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. 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-kappaB 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.
Similar articles
-
The adaptor molecule TIRAP provides signalling specificity for Toll-like receptors.Nature. 2002 Nov 21;420(6913):329-33. doi: 10.1038/nature01180. Nature. 2002. PMID: 12447442
-
Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction.Nature. 2001 Sep 6;413(6851):78-83. doi: 10.1038/35092578. Nature. 2001. PMID: 11544529
-
The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens.Nature. 1999 Oct 21;401(6755):811-5. doi: 10.1038/44605. Nature. 1999. PMID: 10548109
-
Regulation of innate immune responses by Toll-like receptors.Jpn J Infect Dis. 2001 Dec;54(6):209-19. Jpn J Infect Dis. 2001. PMID: 11862002 Review.
-
Toll and Toll-like proteins: an ancient family of receptors signaling infection.Rev Immunogenet. 2000;2(3):294-304. Rev Immunogenet. 2000. PMID: 11256741 Review.
Cited by
-
The main Aeromonas pathogenic factors.ISRN Microbiol. 2012 Sep 4;2012:256261. doi: 10.5402/2012/256261. Print 2012. ISRN Microbiol. 2012. PMID: 23724321 Free PMC article.
-
International Union of Basic and Clinical Pharmacology. XCVI. Pattern recognition receptors in health and disease.Pharmacol Rev. 2015;67(2):462-504. doi: 10.1124/pr.114.009928. Pharmacol Rev. 2015. PMID: 25829385 Free PMC article. Review.
-
Mycobacterium abscessus D-alanyl-D-alanine dipeptidase induces the maturation of dendritic cells and promotes Th1-biased immunity.BMB Rep. 2016 Oct;49(10):554-559. doi: 10.5483/bmbrep.2016.49.10.080. BMB Rep. 2016. PMID: 27439605 Free PMC article.
-
A tug-of-war between the host and the pathogen generates strategic hotspots for the development of novel therapeutic interventions against infectious diseases.Virulence. 2015;6(6):566-80. doi: 10.1080/21505594.2015.1062211. Epub 2015 Jun 24. Virulence. 2015. PMID: 26107578 Free PMC article. Review.
-
Common and specific downstream signaling _targets controlled by Tlr2 and Tlr5 innate immune signaling in zebrafish.BMC Genomics. 2015 Jul 25;16(1):547. doi: 10.1186/s12864-015-1740-9. BMC Genomics. 2015. PMID: 26208853 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
