Historical Background
Toll-like receptors (TLRs) are innate immune receptors that play an important role during infections and diseases. Upon recognition of specific microbe-associated molecular patterns (MAMPs) or self molecules, TLRs initiate signaling cascade that result in the production of pro-inflammatory cytokines, upregulation of co-stimulatory molecules, and molecules necessary for cross-priming of T-cell-dependent immune responses. TLR5 was first reported in humans (Rock et al. 1998), and its location was mapped on chromosome 1. Later in the year 2000, mouse TLR5 was identified and characterized using gene cloning approach (Sebastiani et al. 2000). Hayashi et al., in 2001, showed that innate immune response to bacterial flagellin is mediated through TLR5 (Hayashi et al. 2001). TLR5 recognizes monomeric form of flagella as its ligand and initiates signaling program leading to the activation...
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Andersen-Nissen E, Smith KD, Bonneau R, Strong RK, Aderem A. A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin. J Exp Med. 2007;204(2):393–403.
Atif SM, Uematsu S, Akira S, McSorley SJ. CD103-CD11b+ dendritic cells regulate the sensitivity of CD4 T-cell responses to bacterial flagellin. Mucosal Immunol. 2014;7(1):68–77.
Atif SM, Lee SJ, Li LX, Uematsu S, Akira S, Gorjestani S, Lin X, Schweighoffer E, Tybulewicz VL, McSorley SJ. Rapid CD4+ T-cell responses to bacterial flagellin require dendritic cell expression of Syk and CARD9. Eur J Immunol. 2015;45(2):513–24.
Burdelya LG, Brackett CM, Kojouharov B, Gitlin II, Leonova KI, Gleiberman AS, Aygun-Sunar S, Veith J, Johnson C, Haderski GJ, Stanhope-Baker P, Allamaneni S, Skitzki J, Zeng M, Martsen E, Medvedev A, Scheblyakov D, Artemicheva NM, Logunov DY, Gintsburg AL, Naroditsky BS, Makarov SS, Gudkov AV. Central role of liver in anticancer and radioprotective activities of Toll-like receptor 5 agonist. Proc Natl Acad Sci USA. 2013;110(20):E1857–66.
Chamberlain ND, Vila OM, Volin MV, Volkov S, Pope RM, Swedler W, Mandelin 2nd AM, Shahrara S. TLR5, a novel and unidentified inflammatory mediator in rheumatoid arthritis that correlates with disease activity score and joint TNF-α levels. J Immunol. 2012;189(1):475–83.
Cho KA, Ryu SJ, Park JS, Jang IS, Ahn JS, Kim KT, Park SC. Senescent phenotype can be reversed by reduction of caveolin status. J Biol Chem. 2003;278:27789–95.
Flores-Langarica A, Bobat S, Marshall JL, Yam-Puc JC, Cook CN, Serre K, Kingsley RA, Flores-Romo L, Uematsu S, Akira S, Henderson IR, Toellner KM, Cunningham AF. Soluble flagellin coimmunization attenuates Th1 priming to Salmonella and clearance by modulating dendritic cell activation and cytokine production. Eur J Immunol. 2015;45(8):2299–311.
Franceschi C, Bonafè M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.
Hardenberg G, Yao Y, Piccirillo CA, Levings MK, Steiner TS. Toll-like receptor 5 deficiency protects from wasting disease in a T cell transfer colitis model in T cell receptor-β-deficient mice. Inflamm Bowel Dis. 2012;18(1):85–93.
Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, et al. A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires’ disease. J Exp Med. 2003;198(10):1563–72.
Hawn TR, Scholes D, Li SS, Wang H, Yang Y, Roberts PL, Stapleton AE, Janer M, Aderem A, Stamm WE, Zhao LP, Hooton TM. Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women. PLoS One. 2009;4(6):e5990.
Hayashi F, Smith KD, Ozinsky A, Hawn TR, Yi EC, Goodlett DR, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. 2001;410(6832):1099–103.
Janeway Jr CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216.
Kaden SA, Kurig S, Vasters K, Hofmann K, Zaenker KS, Schmitz J, Winkels G. Enhanced dendritic cell-induced immune responses mediated by the novel C-type lectin receptor mDCAR1. J Immunol. 2009;183:5069–78.
Kassem A, Henning P, Kindlund B, Lindholm C, Lerner UH. TLR5, a novel mediator of innate immunity-induced osteoclastogenesis and bone loss. FASEB J. 2015;29(11):4449–60.
Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373–84.
Kim S-j, Chen Z, Chamberlain ND, Essani AB, Volin MV, Asif Amin M, Volkov S, Gravallese EM, Arami S, Swedler W, Lane NE, Mehta A, Sweiss N, Shahrara S. Ligation of TLR5 promotes myeloid cell infiltration and differentiation into mature osteoclasts in RA and experimental arthritis. J Immunol. 2014;193(8):3902–13.
Letran SE, Lee SJ, Atif SM, Flores-Langarica A, Uematsu S, Akira S, et al. TLR5-deficient mice lack basal inflammatory and metabolic defects but exhibit impaired CD4 T cell responses to a flagellated pathogen. J Immunol. 2011a;186(9):5406–12.
Letran SE, Lee SJ, Atif SM, Uematsu S, Akira S, McSorley SJ. TLR5 functions as an endocytic receptor to enhance flagellin-specific adaptive immunity. Eur J Immunol. 2011b;41(1):29–38.
Lim JS, Nguyen KC, Nguyen CT, Jang IS, Han JM, Fabian C, Lee SE, Rhee JH, Cho KA. Flagellin-dependent TLR5/caveolin-1 as a promising immune activator in immunosenescence. Aging Cell. 2015;14(5):907–15.
McSorley SJ, Ehst BD, Yu Y, Gewirtz AT. Bacterial flagellin is an effective adjuvant for CD4+ T cells in vivo. J Immunol. 2002;169(7):3914–9.
O’Donnell H, Pham OH, Li LX, Atif SM, Lee SJ, Ravesloot MM, Stolfi JL, Nuccio SP, Broz P, Monack DM, Baumler AJ, McSorley SJ. Toll-like receptor and inflammasome signals converge to amplify the innate bactericidal capacity of T helper 1 cells. Immunity. 2014;40(2):213–24.
Oh JZ, Ravindran R, Chassaing B, Carvalho FA, Maddur MS, Bower M, Hakimpour P, Gill KP, Nakaya HI, Yarovinsky F, Sartor RB, Gewirtz AT, Pulendran B. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity. 2014;41(3):478–92.
Plackett TP, Boehmer ED, Faunce DE, Kovacs EJ. Aging and innate immune cells. J Leukoc Biol. 2004;76(2):291–9.
Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF. A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci USA. 1998;95(2):588–93.
Rutkowski MR, Stephen TL, Svoronos N, Allegrezza MJ, Tesone AJ, Perales-Puchalt A, Brencicova E, Escovar-Fadul X, Nguyen JM, Cadungog MG, Zhang R, Salatino M, Tchou J, Rabinovich GA, Conejo-Garcia JR. Microbially driven TLR5-dependent signaling governs distal malignant progression through tumor-promoting inflammation. Cancer Cell. 2015;27(1):27–40.
Sampath V, Garland JS, Le M, Patel AL, Konduri GG, Cohen JD, Simpson PM, Hines RN. A TLR5 (g.1174C > T) variant that encodes a stop codon (R392X) is associated with bronchopulmonary dysplasia. Pediatr Pulmonol. 2012;47(5):460–8.
Sebastiani G, Leveque G, Larivière L, Laroche L, Skamene E, Gros P, Malo D. Cloning and characterization of the murine toll-like receptor 5 (Tlr5) gene: sequence and mRNA expression studies in Salmonella-susceptible MOLF/Ei mice. Genomics. 2000;64(3):230–40.
Singh V, Yeoh BS, Carvalho F, Gewirtz AT, Vijay-Kumar M. Proneness of TLR5 deficient mice to develop colitis is microbiota dependent. Gut Microbes. 2015;6(4):279–83.
Stanley MA. Imiquimod and the imidazoquinolones: mechanism of action and therapeutic potential. Clin Exp Dermatol. 2002;27(7):571–7.
Uematsu S, Akira S. Immune responses of TLR5(+) lamina propria dendritic cells in enterobacterial infection. J Gastroenterol. 2009;44(8):803–11.
Vijay-Kumar M, Aitken JD, Carvalho FA, Cullender TC, Mwangi S, Srinivasan S, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328(5975):228–31.
Zarember KA, Godowski PJ. Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. J Immunol. 2002;168(2):554–61.
Acknowledgment
I thank Prof. Stephen McSorley and Prof. Sangdun Choi for giving me this wonderful opportunity to contribute this book chapter in the second edition of encyclopedia of signaling molecules.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Atif, S.M. (2018). TLR5 (Toll-Like Receptor 5). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_639
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_639
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences