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Toll-like receptor 5

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Template:PBB Toll-like receptor 5, also known as TLR5, is a protein which in humans is encoded by the TLR5 gene.[1] It is a member of the toll-like receptor (TLR) family.

Function

The TLR family plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. TLR5 is expressed on both immune and non-immune cells.[2] TLR5 recognizes bacterial flagellin, a principal component of bacterial flagella and a virulence factor. The activation of this receptor mobilizes the nuclear factor NF-κB and stimulates tumor necrosis factor-alpha production.[3]

TLR5 recognizes flagellin,[4] which is the protein monomer that makes up the filament of bacterial flagella, found on nearly all motile bacteria. There are highly conserved regions in the flagellin protein among all bacteria, facilitating the recognition of flagellin by a germ-line encoded receptor such as TLR5.[5] However, some Proteobacteria flagella have acquired mutations preventing their recognition by TLR5.[6]

Clinical significance

TLR5 may play a role in Inflammatory Bowel Disease (IBD). Statistically significant lower levels of TLR5 expression have been found in patients exhibiting moderate to severe ulcerative colitis (UC). In these patients, lower TLR5 mRNA levels were found along with decreased immunoreactivity of TLR5 in the inflamed mucosa of UC patients.[7]

References

  1. ^ Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF (Jan 1998). "A family of human receptors structurally related to Drosophila Toll". Proceedings of the National Academy of Sciences of the United States of America. 95 (2): 588–93. doi:10.1073/pnas.95.2.588. PMC 18464. PMID 9435236.
  2. ^ Sharma N, Akhade AS, Qadri A (Apr 2013). "Sphingosine-1-phosphate suppresses TLR-induced CXCL8 secretion from human T cells". Journal of Leukocyte Biology. 93 (4): 521–8. doi:10.1189/jlb.0712328. PMID 23345392.
  3. ^ "Entrez Gene: TLR5 toll-like receptor 5".
  4. ^ Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, Eng JK, Akira S, Underhill DM, Aderem A (Apr 2001). "The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5". Nature. 410 (6832): 1099–103. doi:10.1038/35074106. PMID 11323673.
  5. ^ Smith KD, Andersen-Nissen E, Hayashi F, Strobe K, Bergman MA, Barrett SL, Cookson BT, Aderem A (Dec 2003). "Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility". Nature Immunology. 4 (12): 1247–53. doi:10.1038/ni1011. PMID 14625549.
  6. ^ "Evasion of Toll-like receptor 5 by flagellated bacteria". Proceedings of the National Academy of Sciences of the United States of America. 102 (26): 9247–52. Jun 2005. doi:10.1073/pnas.0502040102. PMC 1166605. PMID 15956202. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); More than one of author-name-list parameters specified (help)
  7. ^ "Decreased Toll-like receptor-5 (TLR-5) expression in the mucosa of ulcerative colitis patients". Journal of Physiology and Pharmacology. 60 Suppl 4: 71–5. Oct 2009. PMID 20083854. {{cite journal}}: |first2= missing |last2= (help); |first3= missing |last3= (help); More than one of author-name-list parameters specified (help)

Further reading


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