toll like receptor 5


Summary: A pattern recognition receptor that binds FLAGELLIN. It mediates cellular responses to certain bacterial pathogens.

Top Publications

  1. Kumar A, Yin J, Zhang J, Yu F. Modulation of corneal epithelial innate immune response to pseudomonas infection by flagellin pretreatment. Invest Ophthalmol Vis Sci. 2007;48:4664-70 pubmed
    ..Pre-exposure of the ocular surface to TLR agonists may induce protective mechanisms that not only modulate the host inflammatory response but also provide an innate defense against bacterial infection in the cornea. ..
  2. Burdelya L, Krivokrysenko V, Tallant T, Strom E, Gleiberman A, Gupta D, et al. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models. Science. 2008;320:226-30 pubmed publisher
    ..CBLB502 also showed radioprotective activity in lethally irradiated rhesus monkeys. Thus, TLR5 agonists could potentially improve the therapeutic index of cancer radiotherapy and serve as biological protectants in radiation emergencies...
  3. Deng J, Ma Krupa W, Gewirtz A, Younge B, Goronzy J, Weyand C. Toll-like receptors 4 and 5 induce distinct types of vasculitis. Circ Res. 2009;104:488-95 pubmed publisher
    ..Thus, depending on the original danger signal, vascular DCs edit the emerging immune response by differentially recruiting specialized T effector cells and direct the disease process toward distinct types of vasculitis. ..
  4. McNeilly T, Mitchell M, Nisbet A, McAteer S, Erridge C, Inglis N, et al. IgA and IgG antibody responses following systemic immunization of cattle with native H7 flagellin differ in epitope recognition and capacity to neutralise TLR5 signalling. Vaccine. 2010;28:1412-21 pubmed publisher
    ..coli O157:H7 via neutralisation of TLR5 activation and subsequently reduce vaccine efficacy. ..
  5. Williams M, Bauer S, Lu W, Guo J, Walter S, Bushnell T, et al. Deletion of the mucin-like molecule muc1 enhances dendritic cell activation in response to toll-like receptor ligands. J Innate Immun. 2010;2:123-43 pubmed publisher
  6. Janot L, Sirard J, Secher T, Noulin N, Fick L, Akira S, et al. Radioresistant cells expressing TLR5 control the respiratory epithelium's innate immune responses to flagellin. Eur J Immunol. 2009;39:1587-96 pubmed publisher
    ..We suggest that the radioresistant lung epithelial cells are essential for initiating early, TLR5-dependent signalling in response to flagellin and thus triggering the lung's innate immune responses...
  7. Bannon C, Davies P, Collett A, Warhurst G. Potentiation of flagellin responses in gut epithelial cells by interferon-gamma is associated with STAT-independent regulation of MyD88 expression. Biochem J. 2009;423:119-28 pubmed publisher
    ..The present study adds to our understanding of the spectrum of effects of this cytokine on gut epithelium that may contribute to bacterial-driven inflammation in the gut. ..
  8. Oshima N, Ishihara S, Rumi M, Aziz M, Mishima Y, Kadota C, et al. A20 is an early responding negative regulator of Toll-like receptor 5 signalling in intestinal epithelial cells during inflammation. Clin Exp Immunol. 2010;159:185-98 pubmed publisher
    ..Our results provide new insights into the negative feedback regulation of TLR-5 signalling that maintains the innate immune system in the gut. ..
  9. Mahanonda R, Sa Ard Iam N, Eksomtramate M, Rerkyen P, Phairat B, Schaecher K, et al. Cigarette smoke extract modulates human beta-defensin-2 and interleukin-8 expression in human gingival epithelial cells. J Periodontal Res. 2009;44:557-64 pubmed publisher
    ..Our results represent the first demonstration that CSE can modulate HGEC function by suppressing hBD-2 and enhancing IL-8 production, and this may be, in part, a possible mechanism which promotes periodontal disease. ..

More Information


  1. Thibault S, Imbeault M, Tardif M, Tremblay M. TLR5 stimulation is sufficient to trigger reactivation of latent HIV-1 provirus in T lymphoid cells and activate virus gene expression in central memory CD4+ T cells. Virology. 2009;389:20-5 pubmed publisher
  2. Song L, Zhang Y, Yun N, Poussard A, Smith J, Smith J, et al. Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin. Vaccine. 2009;27:5875-84 pubmed publisher
    ..We find that replacement of domain D3 of flagellin with the VN04 HA globular head creates a highly effective vaccine that elicits protective HAI titers which protect mice against disease and death in a lethal challenge model. ..
  3. Cubillos Ruiz J, Engle X, Scarlett U, Martinez D, Barber A, Elgueta R, et al. Polyethylenimine-based siRNA nanocomplexes reprogram tumor-associated dendritic cells via TLR5 to elicit therapeutic antitumor immunity. J Clin Invest. 2009;119:2231-44 pubmed publisher
  4. Vicente Suarez I, Brayer J, Villagra A, Cheng F, Sotomayor E. TLR5 ligation by flagellin converts tolerogenic dendritic cells into activating antigen-presenting cells that preferentially induce T-helper 1 responses. Immunol Lett. 2009;125:114-8 pubmed publisher
  5. Melkamu T, Squillace D, Kita H, O Grady S. Regulation of TLR2 expression and function in human airway epithelial cells. J Membr Biol. 2009;229:101-13 pubmed publisher
  6. Hafez M, Hayes K, Goldrick M, Grencis R, Roberts I. The K5 capsule of Escherichia coli strain Nissle 1917 is important in stimulating expression of Toll-like receptor 5, CD14, MyD88, and TRIF together with the induction of interleukin-8 expression via the mitogen-activated protein kinase pathway in ep. Infect Immun. 2010;78:2153-62 pubmed publisher
    ..This paper provides new information on the function of the K5 capsule in mediating interactions between Nissle 1917 and epithelial cells and the mechanisms that underlie the probiotic properties of Nissle 1917. ..
  7. Hawn T, Scholes D, Li S, Wang H, Yang Y, Roberts P, et al. Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women. PLoS ONE. 2009;4:e5990 pubmed publisher
    ..Although these data suggest that TLR polymorphisms are associated with adult susceptibility to UTIs, the statistical significance was modest and will require further study including validation with independent cohorts. ..
  8. Choi Y, Im E, Pothoulakis C, Rhee S. TRIF modulates TLR5-dependent responses by inducing proteolytic degradation of TLR5. J Biol Chem. 2010;285:21382-90 pubmed publisher
    ..Collectively, our findings propose a potential inhibitory role of TRIF at least in regulating host-microbial communication via TLR5 in colonic epithelial cells. ..
  9. Kinnebrew M, Ubeda C, Zenewicz L, Smith N, Flavell R, Pamer E. Bacterial flagellin stimulates Toll-like receptor 5-dependent defense against vancomycin-resistant Enterococcus infection. J Infect Dis. 2010;201:534-43 pubmed publisher
    ..By enhancing mucosal resistance to multidrug-resistant organisms, flagellin administration may provide a clinically useful approach to prevent infections in patients treated with broad-spectrum antibiotics. ..
  10. Park C, Lee S, Kim H, Park K, Kim J, Lee S. Synergy of TLR2 and H1R on Cox-2 Activation in Pulpal Cells. J Dent Res. 2010;89:180-5 pubmed publisher
    ..Analysis of these data suggests that TLR2 on pulp fibroblasts, in concert with H1R, can induce an inflammatory response during microbial infection in dental pulp. ..
  11. Campodónico V, Llosa N, Grout M, Doring G, Maira Litran T, Pier G. Evaluation of flagella and flagellin of Pseudomonas aeruginosa as vaccines. Infect Immun. 2010;78:746-55 pubmed publisher
    ..aeruginosa based on flagellar antigens may require additional components beyond type a and type b proteins from prototype strains. ..
  12. House A, Binns M, Gregory S, Catchpole B. Analysis of NOD1, NOD2, TLR1, TLR2, TLR4, TLR5, TLR6 and TLR9 genes in anal furunculosis of German shepherd dogs. Tissue Antigens. 2009;73:250-4 pubmed publisher
    ..The highly restricted PRR genotypes seen in GSD are likely to have resulted from selective breeding and might influence innate immune responses in this breed...
  13. Sirard J, Didierlaurent A, Cayet D, Sierro F, Rumbo M. Toll-like receptor 5- and lymphotoxin beta receptor-dependent epithelial Ccl20 expression involves the same NF-kappaB binding site but distinct NF-kappaB pathways and dynamics. Biochim Biophys Acta. 2009;1789:386-94 pubmed publisher
    ..In summary, different NF-kappaB pathways modulate CCL20 transcription by operating on the same NF-kappaB binding site in the same cell type. ..
  14. Morris A, Liggitt H, Hawn T, Skerrett S. Role of Toll-like receptor 5 in the innate immune response to acute P. aeruginosa pneumonia. Am J Physiol Lung Cell Mol Physiol. 2009;297:L1112-9 pubmed publisher
    ..aeruginosa and contributes to antibacterial resistance in a manner that is partially inoculum dependent. These data are the first to demonstrate a unique role for TLR5 in the innate immune response to P. aeruginosa lung infection. ..
  15. Salazar J, Duhnam Ems S, La Vake C, Cruz A, Moore M, Caimano M, et al. Activation of human monocytes by live Borrelia burgdorferi generates TLR2-dependent and -independent responses which include induction of IFN-beta. PLoS Pathog. 2009;5:e1000444 pubmed publisher
  16. Im J, Jeon J, Cho M, Woo S, Kang S, Yun C, et al. Induction of IL-8 expression by bacterial flagellin is mediated through lipid raft formation and intracellular TLR5 activation in A549 cells. Mol Immunol. 2009;47:614-22 pubmed publisher
  17. Erridge C, Duncan S, Bereswill S, Heimesaat M. The induction of colitis and ileitis in mice is associated with marked increases in intestinal concentrations of stimulants of TLRs 2, 4, and 5. PLoS ONE. 2010;5:e9125 pubmed publisher
    ..We conclude that the induction of colitis or ileitis in mice is associated with significant disease-specific alterations to the PAMP profile of the gut microbiota. ..
  18. Van Maele L, Carnoy C, Cayet D, Songhet P, Dumoutier L, Ferrero I, et al. TLR5 signaling stimulates the innate production of IL-17 and IL-22 by CD3(neg)CD127+ immune cells in spleen and mucosa. J Immunol. 2010;185:1177-85 pubmed publisher
    ..These data define that TLR-induced activation of CD3(neg)CD127(+) cells and production of Th17-related cytokines may be crucial for the early defenses against pathogen invasion of host tissues. ..
  19. Hwang S, Asahi T, Kondo H, Hirono I, Aoki T. Molecular cloning and expression study on Toll-like receptor 5 paralogs in Japanese flounder, Paralichthys olivaceus. Fish Shellfish Immunol. 2010;29:630-8 pubmed publisher
    ..tarda infection, respectively. These results imply that the expression of these TLR 5 paralogs in Japanese flounder are differently regulated in the whole body and play important roles in the immune response against bacterial pathogens. ..
  20. Arikawa K, Nishikawa Y. Interleukin-8 induction due to diffusely adherent Escherichia coli possessing Afa/Dr genes depends on flagella and epithelial Toll-like receptor 5. Microbiol Immunol. 2010;54:491-501 pubmed publisher
    ..Clinically, high motility may be a candidate criterion for predicting the ability of Afa/Dr DAEC strains to induce higher levels of IL-8 secretion. ..
  21. Fournier B, Williams I, Gewirtz A, Neish A. Toll-like receptor 5-dependent regulation of inflammation in systemic Salmonella enterica Serovar typhimurium infection. Infect Immun. 2009;77:4121-9 pubmed publisher
    ..Thus, the characteristic inflammatory pathology of Salmonella infection occurs only in PPs and to a lesser extent in MLN during the initial phases of infection and these early responses are dependent on TLR5. ..
  22. Lapaque N, Muller A, Alexopoulou L, Howard J, Gorvel J. Brucella abortus induces Irgm3 and Irga6 expression via type-I IFN by a MyD88-dependent pathway, without the requirement of TLR2, TLR4, TLR5 and TLR9. Microb Pathog. 2009;47:299-304 pubmed publisher
    ..Our data suggest that Brucella is recognized intracellularly by an unknown receptor, different from the conventional ones used for Gram-negative sensing, but one that nevertheless signals through MyD88...
  23. Vijay Kumar M, Aitken J, Carvalho F, Cullender T, Mwangi S, Srinivasan S, et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science. 2010;328:228-31 pubmed publisher
    ..These results support the emerging view that the gut microbiota contributes to metabolic disease and suggest that malfunction of the innate immune system may promote the development of metabolic syndrome...
  24. de Vos A, Pater J, van den Pangaart P, de Kruif M, Van T Veer C, van der Poll T. In vivo lipopolysaccharide exposure of human blood leukocytes induces cross-tolerance to multiple TLR ligands. J Immunol. 2009;183:533-42 pubmed publisher
  25. Vijay Kumar M, Gewirtz A. Flagellin: key target of mucosal innate immunity. Mucosal Immunol. 2009;2:197-205 pubmed publisher
    ..Discussion will focus on the intestinal tract but will also incorporate key findings in other mucosal surfaces. ..
  26. Yu F, Cornicelli M, Kovach M, Newstead M, Zeng X, Kumar A, et al. Flagellin stimulates protective lung mucosal immunity: role of cathelicidin-related antimicrobial peptide. J Immunol. 2010;185:1142-9 pubmed publisher
  27. Vardarova K, Scharf S, Lang F, Schmeck B, Opitz B, Eitel J, et al. PKC(alpha) and PKC(epsilon) differentially regulate Legionella pneumophila-induced GM-CSF. Eur Respir J. 2009;34:1171-9 pubmed publisher
    ..Thus, differential regulation of GM-CSF, production by PKC isoforms, contributes to the host response in Legionnaires' disease. ..
  28. Aboussahoud W, Bruce C, Elliott S, Fazeli A. Activation of Toll-like receptor 5 decreases the attachment of human trophoblast cells to endometrial cells in vitro. Hum Reprod. 2010;25:2217-28 pubmed publisher
    ..These data suggest a novel mechanism by which the presence of intrauterine infection through TLR5 activation may result in implantation failure. These data may provide a new opportunity in the management of infertility cases. ..
  29. Sun Y, Karmakar M, Roy S, Ramadan R, Williams S, Howell S, et al. TLR4 and TLR5 on corneal macrophages regulate Pseudomonas aeruginosa keratitis by signaling through MyD88-dependent and -independent pathways. J Immunol. 2010;185:4272-83 pubmed publisher
    ..IL-1? and IL-1? are also produced, which activate an IL-1R1/MyD88-positive feedback loop in macrophages and IL-1R on other resident cells in the cornea. ..
  30. Bates J, Uematsu S, Akira S, Mizel S. Direct stimulation of tlr5+/+ CD11c+ cells is necessary for the adjuvant activity of flagellin. J Immunol. 2009;182:7539-47 pubmed publisher
  31. de Zoete M, Keestra A, Wagenaar J, van Putten J. Reconstitution of a functional Toll-like receptor 5 binding site in Campylobacter jejuni flagellin. J Biol Chem. 2010;285:12149-58 pubmed publisher
    ..Overall, our results reveal a novel structural requirement for TLR5 recognition of bacterial flagellin and exclude flagellin glycosylation as an additional mechanism of bacterial evasion of the TLR5 response. ..
  32. Metcalfe H, Best A, Kanellos T, La Ragione R, Werling D. Flagellin expression enhances Salmonella accumulation in TLR5-positive macrophages. Dev Comp Immunol. 2010;34:797-804 pubmed publisher
    ..This study suggests that flagellin may be inducing TLR5-dependent internalisation mechanisms in Mcapital EF, Cyrillic which vary qualitatively between different species and Salmonella serotypes. ..
  33. Choi Y, Im E, Chung H, Pothoulakis C, Rhee S. TRIF mediates Toll-like receptor 5-induced signaling in intestinal epithelial cells. J Biol Chem. 2010;285:37570-8 pubmed publisher
    ..Our findings suggest an important role of TRIF in regulating host-microbial communication via TLR5 in the gut epithelium. ..
  34. Galli R, Starace D, Busà R, Angelini D, Paone A, De Cesaris P, et al. TLR stimulation of prostate tumor cells induces chemokine-mediated recruitment of specific immune cell types. J Immunol. 2010;184:6658-69 pubmed publisher
  35. Young S, Lyddon T, Jorgenson R, Misfeldt M. Expression of Toll-like receptors in human endometrial epithelial cells and cell lines. Am J Reprod Immunol. 2004;52:67-73 pubmed
    ..These studies provide the first evidence of TLR expression in the endometrium of any species and suggest the usefulness of endometrial cell lines to study TLR function. ..
  36. Raoust E, Balloy V, Garcia Verdugo I, Touqui L, Ramphal R, Chignard M. Pseudomonas aeruginosa LPS or flagellin are sufficient to activate TLR-dependent signaling in murine alveolar macrophages and airway epithelial cells. PLoS ONE. 2009;4:e7259 pubmed publisher
    ..Either ligand/receptor pair is sufficient to sense the bacterium and to trigger cell activation, and when both are missing lung EC and AM are unable to produce such a response as were cells from MyD88(-/-) mice. ..
  37. Sanchez E, Callejas Rubio J, Sabio J, Gonzalez Gay M, Jimenez Alonso J, Mico L, et al. Investigation of TLR5 and TLR7 as candidate genes for susceptibility to systemic lupus erythematosus. Clin Exp Rheumatol. 2009;27:267-71 pubmed
    ..08). These results suggest that the tested variations of TLR5 and TLR7 genes do not confer a relevant role in the susceptibility or severity to SLE in the Spanish population. ..
  38. Abtin A, Eckhart L, Gläser R, Gmeiner R, Mildner M, Tschachler E. The antimicrobial heterodimer S100A8/S100A9 (calprotectin) is upregulated by bacterial flagellin in human epidermal keratinocytes. J Invest Dermatol. 2010;130:2423-30 pubmed publisher
    ..coli induced the expression of S100A8 and S100A9. Our data suggest that bacterial flagellin induces the upregulation of S100A8/S100A9 via a TLR5-dependent mechanism in epidermal KCs. ..
  39. Ben Yebdri F, Kukulski F, Tremblay A, Sevigny J. Concomitant activation of P2Y(2) and P2Y(6) receptors on monocytes is required for TLR1/2-induced neutrophil migration by regulating IL-8 secretion. Eur J Immunol. 2009;39:2885-94 pubmed publisher
    ..In line with our previous work on TLR4, this study further supports the importance of nucleotides in bacterial-induced neutrophil migration. ..
  40. Muñoz N, Van Maele L, Marqués J, Rial A, Sirard J, Chabalgoity J. Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection. Infect Immun. 2010;78:4226-33 pubmed publisher
    ..In conclusion, this study emphasizes that mucosal stimulation of innate immunity by a TLR not naturally engaged by S. pneumoniae can increase the potential to cure pneumococcal pneumonia. ..
  41. Uematsu S, Akira S. Immune responses of TLR5(+) lamina propria dendritic cells in enterobacterial infection. J Gastroenterol. 2009;44:803-11 pubmed publisher
    ..These LPDCs have unique properties in that they can induce acquired immunity as well as innate immunity via TLR5 in the intestine. ..
  42. Gao N, Kumar A, Jyot J, Yu F. Flagellin-induced corneal antimicrobial peptide production and wound repair involve a novel NF-kappaB-independent and EGFR-dependent pathway. PLoS ONE. 2010;5:e9351 pubmed publisher
  43. Stanislawowski M, Wierzbicki P, Golab A, Adrych K, Kartanowicz D, Wypych J, et al. Decreased Toll-like receptor-5 (TLR-5) expression in the mucosa of ulcerative colitis patients. J Physiol Pharmacol. 2009;60 Suppl 4:71-5 pubmed
  44. Lim D, Narasimhan S, Michaylira C, Wang M. TLR3-mediated NF-{kappa}B signaling in human esophageal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2009;297:G1172-80 pubmed publisher
    ..Our findings demonstrate for the first time that TLR3 is highly functional in the human esophageal epithelium and that TLR3-mediated NF-kappaB signaling may play an important regulatory role in esophageal epithelial homeostasis. ..
  45. Ivison S, Himmel M, Hardenberg G, Wark P, Kifayet A, Levings M, et al. TLR5 is not required for flagellin-mediated exacerbation of DSS colitis. Inflamm Bowel Dis. 2010;16:401-9 pubmed publisher
    ..Moreover, we found that DSS colitis was more severe in TLR5(-/-) mice than wildtype C57BL/6 mice. Together, these results suggest that flagellin-mediated exacerbation of colitis is independent of TLR5. ..
  46. Posadas S, Caz V, Caballero I, Cendejas E, Quilez I, Largo C, et al. Effects of mannoprotein E1 in liquid diet on inflammatory response and TLR5 expression in the gut of rats infected by Salmonella typhimurium. BMC Gastroenterol. 2010;10:58 pubmed publisher
    ..These results could open up new avenues in the use of mannoproteins as prebiotics in the therapeutic strategy for treatment of inflammatory gut processes induced by microbia. ..
  47. Rydberg C, Mansson A, Uddman R, Riesbeck K, Cardell L. Toll-like receptor agonists induce inflammation and cell death in a model of head and neck squamous cell carcinomas. Immunology. 2009;128:e600-11 pubmed publisher
    ..A similar response was not seen in normal epithelial cells. Thus, the TLR system should be considered an important target in future antitumour immunotherapy. ..
  48. Bartfeld S, Engels C, Bauer B, Aurass P, Flieger A, Bruggemann H, et al. Temporal resolution of two-tracked NF-kappaB activation by Legionella pneumophila. Cell Microbiol. 2009;11:1638-51 pubmed publisher
    ..Our data underline the strong connection between NF-kappaB activation and intracellular replication and hints at an active interference of NF-kappaB signalling by L. pneumophila. ..
  49. Guo Y, Zhao G, Tanaka S, Yamaguchi T. Differential responses between monocytes and monocyte-derived macrophages for lipopolysaccharide stimulation of calves. Cell Mol Immunol. 2009;6:223-9 pubmed publisher
    ..Besides, no expression of TLR9 was found. As antigen presenting cells, monocytes and monocyte-derived macrophages respond differently to LPS, so they may have different functions in the innate immune system. ..
  50. Biswas B, Narmadha G, Choudhary M, French F, Hall S, Yenugu S. Identification of Toll-like receptors in the rat (Rattus norvegicus): messenger RNA expression in the male reproductive tract under conditions of androgen variation. Am J Reprod Immunol. 2009;62:243-52 pubmed publisher
    ..Tlrs seem to be expressed during male reproductive tract development and under conditions of androgen ablation, suggesting the preparedness of the male reproductive tract to detect an infection under all conditions of androgen status. ..
  51. Buzzo C, Campopiano J, Massis L, Lage S, Cassado A, Leme Souza R, et al. A novel pathway for inducible nitric-oxide synthase activation through inflammasomes. J Biol Chem. 2010;285:32087-95 pubmed publisher
    ..Together, our data defined an additional anti-pathogen effector mechanism operated through Naip5 and Nlrc4 inflammasomes and illustrated a novel signaling transduction pathway that activates iNOS. ..