Abstract
Toll-like receptor (TLR) 2 is a member of the vertebrate protein family of TLRs that has been studied in substantial detail over the last years. The extracellular domain of the type I receptor molecule TLR2 contains 18 to 20 leucine rich repeat (LRR) and LRR like motives. The intracellular domain of TLR2 contains a Toll/IL-1 receptor/resistance protein typical TIR domain. After the first implication of TLR4 in immunity thereinafter followed by the discovery of the lipopolysaccharide signal transducer function of TLR4, TLR2 was the first of ten mammalian TLRs proven to be directly involved in recognition of pathogen associated molecular patterns (PAMPs). Among the TLR2 specific agonists are microbial products representing broad groups of species such as Gram-positive and Gram-negative bacteria, as well as mycobacteria, spirochetes, and mycoplasm. PAMP induced phagosomal localization of TLR2 and TLR2 dependent apoptosis have been shown. Complex formation with other molecules involved in pattern recognition such as CD14, MD2, TLR1, and TLR6 has been implicated for TLR2. Surprisingly even proteinaceous host material such as heat shock protein (HSP) 60 has been demonstrated to activate cells through TLR2. Thus, TLR2 may be a sensor and inductor of specific defense processes, including oxidative stress and cellular necrosis initially spurred by microbial compounds. Here we summarize the current knowledge on the structure and function of TLR2, which is far from being complete. Detailed understanding of the biology of TLR2 will probably contribute to the characterization of a number of infectious diseases and potentially help in the development of novel intervention strategies.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aderem A, Ulevitch RJ (2000) Toll-like receptors in the induction of the innate immune response. Nature 406: 782–7
Ahmed R, Gray D (1996) Immunological memory and protective immunity: understanding their relation. Science 272: 54–60
Akashi S, Nagai Y, Ogata H, Oikawa M, Fukase K, Kusumoto S, Kawasaki K, Nishijima M, Hayashi S, Kimoto M, Miyake K (2001) Human MD-2 confers on mouse Toll-like receptor 4 species-specific lipopolysaccharide recognition. Int Immunol 13: 1595–9
Alexopoulou L, Holt AC, Medzhitov R, Flavell RA (2001) Recognition of double-stranded RNA and activation of NF-KB by Toll-like receptor 3. Nature 413: 732–8
Aliprantis AO, Yang RB, Mark MR, Suggett S, Devaux B, Radolf JD, Klimpel GR, Godowski P, Zychlinsky A (1999) Cell activation and apoptosis by bacterial lipoproteins through toll-like receptor- 2. Science 285: 736–9
Aliprantis AO, Yang RB, Weiss DS, Godowski P, Zychlinsky A (2000) The apoptotic signaling pathway activated by Toll-like receptor-2. Embo J 19: 3325–36
Arbibe L, Mira JP, Teusch N, Kline L, Guha M, Mackman N, Godowski PJ, Ulevitch RJ, Knaus UG (2000) Toll-like receptor 2-mediated NF-K B activation requires a Racl-dependent pathway. Nat Immunol 1: 533–40
Asai Y, Ohyama Y, Gen K, Ogawa T (2001) Bacterial fimbriae and their peptides activate human gingival epithelial cells through Toll-like receptor 2. Infect Immun 69: 7387–95
Baeuerle PA, Baltimore D (1996) NF-K B: ten years after. Cell 87: 13–20
Bauer S, Kirschning CJ, Hacker H, Redecke V, Hausmann S, Akira S, Wagner H, Lipford GB (2001) Human TLR9 confeis responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci U S A 98: 9237–42
Belvin MP, Anderson KV (1996) A conserved signaling pathway: the Drosophila toll-dorsal pathway. Annu Rev Cell Dev Biol 12: 393–416
Bessler WG, Jung G 1992 Synthetic lipopeptides as novel adjuvants. Res Immunol 143:548–53; discussion 579–80
Birchler T, Seibl R, Buchner K, Loeliger S, Seger R, Hossle JP, Aguzzi A, Lauener RP (2001) Human Toll-like receptor 2 mediates induction of the antimicrobial peptide human beta-defensin 2 in response to bacterial lipoprotein. Eur J Immunol 31: 3131–7
Blease K, Kunkel SL, Hogaboam CM (2001) IL-18 modulates chronic fungal asthma in a murine model; putative involvement of Toll-like receptor-2. Inflamm Res 50: 552–60
Bone RC (1994) Gram-positive organisms and sepsis. Arch Intern Med 154: 26–34
Borges MM, Campos-Neto A, Sleath P, Grabstein KH, Morrissey PJ, Skeiky YA, Reed SG (2001) Potent stimulation of the innate immune system by a Leishmania brasiliensis recombinant protein. Infect Immun 69: 5270–7
Boyd Y, Goodchild M, Morroll S, Bumstead N (2001) Mapping of the chicken and mouse genes for toll¬like receptor 2 (TLR2) to an evolutionarily conserved chromosomal segment. Immunogenetics 52: 294–8
Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT, Bleharski JR, Maitland M, Norgard MV, Plevy SE, Smale ST, Brennan PJ, Bloom BR, Godowski PJ, Modlin RL (1999) Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 285: 732–6
Campos MA, Almeida IC, Takeuchi O, Akira S, Valente EP, Procopio DO, Travassos LR, Smith JA, Golenbock DT, Gazzinelli RT (2001) Activation of Toll-like receptor-2 by glycosylphosphatidyli- nositol anchors from a protozoan parasite. J Immunol 167: 416–23
Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV (1996) TRAF6 is a signal transducer for interleukin-1. Nature 383: 443–6
Cario E, Podolsky DK (2000) Differential alteration in intestinal epithelial cell expression of toll-like receptor 3 (TLR3) and TLR4 in inflammatory bowel disease. Infect Immun 68: 7010–7
Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410: 37–40
Chaudhary PM, Ferguson C, Nguyen V, Nguyen O, Massa HF, Eby M, Jasmin A, Trask BJ, Hood L, Nelson PS (1998) Cloning and characterization of two Toll/Interleukin-1 receptor-like genes TIL3 and TIL4: evidence for a multi-gene receptor family in humans. Blood 91: 4020–7
Chuang T, Ulevitch RJ (2001) Identification of hTLRlO: a novel human Toll-like receptor preferentially expressed in immune cells. Biochim Biophys Acta 1518: 157–61
da Silva Correia J, Soldau K, Christen U, Tobias PS, Ulevitch RJ (2001) Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex, transfer from CD 14 to TLR4 and MD-2. J Biol Chem 276: 21129–35
De Kimpe SJ, Kengatharan M, Thiemermann C, Vane JR (1995) The cell wall components peptidoglycan and lipoteichoic acid from Staphylococcus aureus act in synergy to cause shock and multiple organ failure. Proc Natl Acad Sci USA 92: 10359–63
Dziarski R, Wang Q, Miyake K, Kirschning CJ, Gupta D (2001) MD-2 enables Toll-like receptor 2 (TLR2)-mediated responses to lipopolysaccharide and enhances TLR2-mediated responses to Gram- positive and Gram-negative bacteria and their cell wall components. J Immunol 166: 1938–44
Ehrt S, Schnappinger D, Bekiranov S, Drenkow J, Shi S, Gingeras TR, Gaasterland T, Schoolnik G, Nathan C (2001) Reprogramming of the macrophage transcriptome in response to interferon-gamma and Mycobacterium tuberculosis: signaling roles of nitric oxide synthase-2 and phagocyte oxidase. J Exp Med 194: 1123–40
Faure E, Thomas L, Xu H, Medvedev A, Equils O, Arditi M (2001) Bacterial lipopolysaccharide and IFN-gamma induce Toll-like receptor 2 and Toll-like receptor 4 expression in human endothelial cells: role of NF-kappa B activation. J Immunol 166: 2018–24
Fearon DT, Locksley RM (1996) The instructive role of innate immunity in the acquired immune response. Science 272: 50–3
Fischer W (2000) Phosphocholine of pneumococcal teichoic acids: role in bacterial physiology and pneumococcal infection. Res Microbiol 151: 421–7
Flo TH, Halaas O, Torp S, Ryan L, Lien E, Dybdahl B, Sundan A, Espevik T (2001) Differential expression of Toll-like receptor 2 in human cells. J Leukoc Biol 69: 474–81
Frantz S, Kelly RA, Bourcier T (2001) Role of TLR-2 in the activation of nuclear factor KB by oxidative stress in cardiac myocytes. J Biol Chem 276: 5197–203
Frendeus B, Wachtler C, Hedlund M, Fischer H, Samuelsson P, Svensson M, Svanborg C (2001) Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation. Mol Microbiol 40: 37–51
Golenbock DT, Fenton MJ (2001) Extolling the diversity of bacterial endotoxins. Nat Immunol 2:286-8 Heine H, Kirschning CJ, Lien E, Monks BG, Rothe M, Golenbock DT (1999) Cutting edge: cells that carry A null allele for toll-like receptor 2 are capable of responding to endotoxin. J Immunol 162: 6971–5
Heine H, Kirschning CJ, Lien E, Monks BG, Rothe M, Golenbock DT (1999) Cutting edge: cells that carry A null allele for toll-like receptor 2 are capable for responding to endotoxin. J Immunol 161:6971–5
Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408: 740–5
Henneke P, Takeuchi O, van Strijp JA, Guttormsen HK, Smith JA, Schromm AB, Espevik TA, Akira S, Nizet V, Kasper DL, Golenbock DT (2001) Novel engagement of CD 14 and multiple toll-like receptors by group B streptococci. J Immunol 167: 7069–76
Heumann D, Barras C, Severin A, Glauser MP, Tomasz A (1994) Gram-positive cell walls stimulate synthesis of tumor necrosis factor alpha and interleukin-6 by human monocytes. Infect Immun 62: 2715–21
Hirschfeld M, Kirschning CJ, Schwandner R, Wesche H, Weis JH, Wooten RM, Weis JJ (1999) Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by toll-like receptor 2. J Immunol 163: 2382–6
Hirschfeld M, Ma Y, Weis JH, Vogel SN, Weis JJ (2000) Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J Immunol 165: 618–22
Hirschfeld M, Weis JJ, Toshchakov V, Salkowski CA, Cody MJ, Ward DC, Qureshi N, Michalek SM, Vogel SN (2001) Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect Immun 69: 1477–82
Hoshino K, Takeuchi O, Kawai T, Sanjo H, Ogawa T, Takeda Y, Takeda K, Akira S (1999) Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162: 3749–52
Ip YT, Davis RJ (1998) Signal transduction by the c-Jun N-terminal kinase (JNK)-from inflammation to development. Curr Opin Cell Biol 10: 205–19
Johnson RC (1977) The spirochetes. Annu Rev Microbiol 31: 89–106
Kajava AV (1998) Structural diversity of leucine-rich repeat proteins. J Mol Biol 277: 519–27
Kang TJ, Chae GT (2001) Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous leprosy patients. FEMS Immunol Med Microbiol 31: 53–8
Kirschning CJ, Bauer S (2001) Toll-like receptors: cellular signal transducers for exogenous molecular patterns causing immune responses. Int J Med Microbiol 291: 251–60
Kirschning CJ, Wesche H, Merrill Ayres T, Rothe M (1998) Human toll-like receptor 2 confers responsiveness to bacterial lipopolysaccharide. J Exp Med 188: 2091–7
Kobe B, Deisenhofer J (1994) The leucine-rich repeat: a versatile binding motif. Trends Biochem Sci 19: 415–21
Kol A, Sukhova GK, Lichtman AH, Libby P (1998) Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression. Circulation 98: 300–7
Laflamme N, Soucy G, Rivest S (2001) Circulating cell wall components derived from gram-negative, not gram-positive, bacteria cause a profound induction of the gene-encoding Toll-like receptor 2 in the CNS. J Neurochem 79: 648–57
Lee JY, Sohn KH, Rhee SH, Hwang D (2001) Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4. J Biol Chem 276: 16683–9
Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (1996) The dorsoventral regulatory gene cassette spatzle/Toll/cactus controls the potent antifungal response in Drosophila adults. Cell 86: 973–83
Li M, Carpio DF, Zheng Y, Bruzzo P, Singh V, Ouaaz F, Medzhitov RM, Beg AA (2001) An essential role of the NF-KB/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells. J Immunol 166: 7128–35
Liu C, Xu Z, Gupta D, Dziarski R (2001) Peptidoglycan recognition proteins: a novel family of four human innate immunity pattern recognition molecules. J Biol Chem 276: 34686–94
Lomaga MA, Yeh WC, Sarosi I, Duncan GS, Furlonger C, Ho A, Morony S, Capparelli C, Van G, Kaufman S, van der Heiden A, Itie A, Wakeham A, Khoo W, Sasaki T, Cao Z, Penninger JM, Paige CJ, Lacey DL, Dunstan CR, Boyle WJ, Goeddel DV, Mak TW (1999) TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 13: 1015–24
Lorenz E, Mira JP, Cornish KL, Arbour NC, Schwartz DA (2000) A novel polymorphism in the toll-like receptor 2 gene and its potential association with staphylococcal infection. Infect Immun 68: 6398–401
Martin M, Katz J, Vogel SN, Michalek SM (2001) Differential induction of endotoxin tolerance by lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli. J Immunol 167: 5278–85
Massari P, Henneke P, Ho Y, Latz E, Golenbock DT, Wetzler LM (2002) Cutting Edge: Immune Stimulation by Neisserial Porins Is Toll-Like Receptor 2 and MyD88 Dependent. J Immunol 168: 1533–1537
Matsuguchi T, Musikacharoen T, Ogawa T, Yoshikai Y (2000a) Gene expressions of Toll-like receptor 2, but not Toll-like receptor 4, is induced by LPS and inflammatory cytokines in mouse macrophages. J Immunol 165: 5767–72
Matsuguchi T, Takagi K, Musikacharoen T, Yoshikai Y (2000b) Gene expressions of lipopolysaccharide receptors, toll-like receptors 2 and 4, are differently regulated in mouse T lymphocytes. Blood 95: 1378–85
Means TK, Wang S, Lien E, Yoshimura A, Golenbock DT, Fenton MJ (1999) Human toll-like receptors mediate cellular activation by Mycobacterium tuberculosis. J Immunol 163: 3920–7
Medzhitov R, Janeway CA (1997) Innate immunity: the virtues of a nonclonal system of recognition. Cell 91: 295–8
Medzhitov R, Preston-Hurlburt P, Janeway CA, Jr (1997) A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature 388: 394–7
Michel T, Reichhart JM, Hoffmann JA, Royet J (2001) Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein. Nature 414: 756–9
Michelsen KS, Aicher A, Mohaupt M, Hartung T, Dimmeler S, Kirschning CJ, Schumann RR (2001) The role of toll-like receptors (TLRs) in bacteria-induced maturation of murine dendritic cells (DCS). Peptidoglycan and lipoteichoic acid are inducers of DC maturation and require TLR2. J Biol Chem 276: 25680–6
Mita Y, Dobashi K, Shimizu Y, Nakazawa T, Mori M (2001) Toll-like receptor 2 and 4 surface expressions on human monocytes are modulated by interferon-gamma and macrophage colony- stimulating factor. Immunol Lett 78: 97–101
Mitcham JL, Parnet P, Bonnert TP, Garka KE, Gerhart MJ, Slack JL, Gayle MA, Dower SK, Sims JE (1996) T1/ST2 signaling establishes it as a member of an expanding interleukin-1 receptor family. J Biol Chem 271: 5777–83
Mokuno Y, Matsuguchi T, Takano M, Nishimura H, Washizu J, Ogawa T, Takeuchi O, Akira S, Nimura Y, Yoshikai Y (2000) Expression of toll-like receptor 2 on gamma delta T cells bearing invariant V gamma 6/V delta 1 induced by Escherichia coli infection in mice. J Immunol 165: 931–40
Morath S, Geyer A, Hartung T (2001) Structure-Function Relationship of Cytokine Induction by Lipoteichoic Acid from Staphylococcus aureus. J Exp Med 193: 393–8
Muhlradt PF, Kiess M, Meyer H, Sussmuth R, Jung G (1997) Isolation, structure elucidation, and synthesis of a macrophage stimulatory lipopeptide from Mycoplasma fermentans acting at picomolar concentration. J Exp Med 185: 1951–8
Murakami S, Iwaki D, Mitsuzawa H, Sano H, Takahashi H, Voelker DR, Akino T, Kuroki Y (2001) Surfactant protein A inhibits peptidoglycan-induced TNF-alpha secretion in U937 cells and alveolar macrophages by direct interaction with toll-like receptor 2. J Biol Chem 27: 27
Musikacharoen T, Matsuguchi T, Kikuchi T, Yoshikai Y (2001) NF-KB and STAT5 play important roles in the regulation of mouse Toll-like receptor 2 gene expression. J Immunol 166: 4516–24
Muzio M, Bosisio D, Polentarutti N, D’Amico G, Stoppacciaro A, Mancinelli R, van’t Veer C, Penton- Rol G, Ruco LP, Allavena P, Mantovani A (2000) Differential expression and regulation of toll-like receptors (TLR) in human leukocytes: selective expression of TLR3 in dendritic cells. J Immunol 164: 5998–6004
Muzio M, Natoli G, Saccani S, Levrero M, Mantovani A (1998) The human toll signaling pathway: divergence of nuclear factor KB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6). J Exp Med 187: 2097–101
Muzio M, Ni J, Feng P, Dixit VM (1997) IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling. Science 278:1612-5 O’Neill LA, Dinarello CA (2000) The IL-1 receptor/toll-like receptor superfamily: crucial receptors for inflammation and host defense. Immunol Today 21: 206–9
O’Neil LA, Dinarello CA (2000) The IL-1 receptor/toll-like receptor superfamily: crucial receptors for inflammation and host defense. Immunol Today 21:206–9
Ohashi K, Burkart V, Flohe S, Kolb H (2000) Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 164: 558–61
Opitz B, Schroder NW, Spreitzer I, Michelsen KS, Kirschning CJ, Hallatschek W, Zahringer U, Hartung T, Gobel UB, Schumann RR (2001) Toll-like receptor-2 mediates Treponema glycolipid and lipoteichoic acid-induced NF-KB translocation. J Biol Chem 276: 22041–7
Ozinsky A, Underhill DM, Fontenot JD, Hajjar AM, Smith KD, Wilson CB, Schroeder L, Aderem A (2000) The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors. Proc Natl Acad Sci USA 97: 13766–71
Pfeiffer A, Bottcher A, Orso E, Kapinsky M, Nagy P, Bodnar A, Spreitzer I, Liebisch G, Drobnik W, Gempel K, Horn M, Holmer S, Hartung T, Multhoff G, Schutz G, Schindler H, Ulmer AJ, Heine H, Stelter F, Schutt C, Rothe G, Szollosi J, Damjanovich S, Schmitz G (2001) Lipopolysaccharide and ceramide docking to CD 14 provokes ligand-specific receptor clustering in rafts. Eur J Immunol 31: 3153–64
Poltorak A, He X, Smirnova I, Liu MY, Huffel CV, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B (1998) Defective LPS signaling in C3H/ HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282: 2085–8
Porcella SF, Schwan TG (2001) Borrelia burgdorferi and Treponema pallidum: a comparison of functional genomics, environmental adaptations, and pathogenic mechanisms. J Clin Invest 107: 651–6
Prebeck S, Kirschning C, Durr S, da Costa C, Donath B, Brand K, Redecke V, Wagner H, Miethke T (2001) Predominant role of toll-like receptor 2 versus 4 in Chlamydia pneumoniae-induced activation of dendritic cells. J Immunol 167: 3316–23
Pulendran B, Kumar P, Cutler CW, Mohamadzadeh M, Van Dyke T, Banchereau J (2001) Lipopolysaccharides from distinct pathogens induce different classes of immune responses in vivo. J Immunol 167: 5067–76
Qureshi ST, Lariviere L, Leveque G, Clermont S, Moore KJ, Gros P, Malo D (1999) Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4). J Exp Med 189: 615–25
Rietschel ET, Brade H, Hoist O, Brade L, Muller-Loennies S, Mamat U, Zahringer U, Beckmann F, Seydel U, Brandenburg K, Ulmer AJ, Mattern T, Heine H, Schletter J, Loppnow H, Schonbeck U, Flad HD, Hauschildt S, Schade UF, Di Padova F, Kusumoto S, Schumann RR (1996) Bacterial endotoxin: Chemical constitution, biological recognition, host response, and immunological detoxification. Curr Top Microbiol Immunol 216: 39–81
Riviere GR, Wagoner MA, Baker-Zander SA, Weisz KS, Adams DF, Simonson L, Lukehart SA (1991) Identification of spirochetes related to Treponema pallidum in necrotizing ulcerative gingivitis and chronic periodontitis. N Engl J Med 325: 539–43
Rock FL, Hardiman G, Timans JC, Kastelein RA, Bazan JF (1998) A family of human receptors structurally related to Drosophila Toll. Proc Natl Acad Sci USA 95: 588–93
Rothe M, Wong SC, Henzel WJ, Goeddel DV (1994) A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor. Cell 78: 681–92
Sato S, Nomura F, Kawai T, Takeuchi O, Muhlradt PF, Takeda K, Akira S (2000) Synergy and cross- tolerance between toll-like receptor (TLR) 2- and TLR4-mediated signaling pathways. J Immunol 165: 7096–101
Schleifer KH, Kandler O (1972) Peptidoglycan types of bacterial cell walls and their taxonomic implications. Bacteriol Rev 36: 407–77
Schroder NW, Opitz B, Lamping N, Michelsen KS, Zahringer U, Gobel UB, Schumann RR (2000) Involvement of lipopolysaccharide binding protein, CD 14, and Toll-like receptors in the initiation of innate immune responses by Treponema glycolipids. J Immunol 165: 2683–93
Schroder NW, Pfeil D, Opitz B, Michelsen KS, Amberger J, Zahringer U, Gobel UB, Schumann RR (2001) Activation of mitogen-activated protein kinases p42/44, p38, and stress-activated protein kinases in myelo-monocytic cells by Treponema lipoteichoic acid. J Biol Chem 276: 9713–9
Schultz J, Milpetz F, Bork P, Ponting CP (1998) SMART, a simple modular architecture research tool: identification of signaling domains. Proc Natl Acad Sci USA 95: 5857–64
Schumann RR, Leong SR, Flaggs GW, Gray PW, Wright SD, Mathison JC, Tobias PS, Ulevitch RJ (1990) Structure and function of lipopolysaccharide binding protein. Science 249: 1429–31
Schwandner R, Dziarski R, Wesche H, Rothe M, Kirschning CJ (1999) Peptidoglycan and lipoteichoic acid-induced cell activation is mediated by toll-like receptor 2. J Biol Chem 274: 17406–9
Shuto T, Xu H, Wang B, Han J, Kai H, Gu XX, Murphy TF, Lim DJ, Li JD (2001) Activation of NF-KB by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK- IKK alpha /beta-I KB alpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells. Proc Natl Acad Sci USA 98: 8774–9
Silverman N, Maniatis T (2001) NF-KB signaling pathways in mammalian and insect innate immunity. Genes Dev 15: 2321–42
Song HY, Regnier CH, Kirschning CJ, Goeddel DV, Rothe M (1997) Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-icB and c-jun N-terminal kinase (JNK/ SAPK) pathways at TNF receptor-associated factor 2. Proc Natl Acad Sci USA 94: 9792–6
Takeuchi O, Hoshino K, Kawai T, Sanjo H, Takada H, Ogawa T, Takeda K, Akira S (1999) Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components. Immunity 11: 443–51
Takeuchi O, Hoshino K, Akira S (2000) Cutting edge: TLR2-deficient and MyD88-deficient mice are highly susceptible to Staphylococcus aureus infection. J Immunol 165: 5392–6
Takeuchi O, Kawai T, Muhlradt PF, Morr M, Radolf JD, Zychlinsky A, Takeda K, Akira S (2001) Discrimination of bacterial lipoproteins by Toll-like receptor 6. Int Immunol 13: 933–40
Thoma-Uszynski S, Stenger S, Takeuchi O, Ochoa MT, Engele M, Sieling PA, Barnes PF, Rollinghoff M, Bolcskei PL, Wagner M, Akira S, Norgard MV, Belisle JT, Godowski PJ, Bloom BR, Modlin RL (2001) Induction of direct antimicrobial activity through mammalian toll-like receptors. Science 291: 1544–7
Ulevitch RJ, Tobias PS (1995) Receptor-dependent mechanisms of cell stimulation by bacterial endotoxin. Annu Rev Immunol 13: 437–57
Underhill DM, Ozinsky A, Hajjar AM, Stevens A, Wilson CB, Bassetti M, Aderem A (1999a) The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401: 811–5
Underhill DM, Ozinsky A, Smith KD, Aderem A (1999b) Toll-like receptor-2 mediates mycobacteria induced proinflammatory signaling in macrophages. Proc Natl Acad Sci USA 96: 14459–63
Vabulas RM, Ahmad-Nejad P, da Costa C, Miethke T, Kirschning CJ, Hacker H, Wagner H (2001) Endocytosed HSP60 s use toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem 276: 31332–9
Visintin A, Mazzoni A, Spitzer JH, Wyllie DH, Dower SK, Segal DM (2001) Regulation of Toll-like receptors in human monocytes and dendritic cells. J Immunol 166: 249–55
Vogel G (1998) Fly development genes lead to immune find. Science 281: 1942 – 4
Wang T, Lafuse WP, Zwilling BS (2001) NFKB and Spl elements are necessary for maximal transcription of toll-like receptor 2 induced by Mycobacterium avium. J Immunol 167: 6924–32
Werts C, Tapping RI, Mathison JC, Chuang TH, Kravchenko V, Saint Girons I, Haake DA, Godowski PJ, Hayashi F, Ozinsky A, Underhill DM, Kirschning CJ, Wagner H, Aderem A, Tobias PS, Ulevitch RJ (2001) Leptospiral lipopolysaccharide activates cells through a TLR2-dependent mechanism. Nat Immunol 2: 346–52
Wesche H, Henzel WJ, Shillinglaw W, Li S, Cao Z (1997) MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7: 837–47
Williams MJ, Rodriguez A, Kimbrell DA, Eldon ED (1997) The 18-wheeler mutation reveals complex antibacterial gene regulation in Drosophila host defense. Embo J 16: 6120–30
Wooten RM, Ma Y, Yoder RA, Brown JP, Weis JH, Zachary JF, Kirschning CJ, Weis JJ (2002) Toll-like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi. J Immunol 168: 348–55
Wright SD, Ramos RA, Tobias PS, Ulevitch RJ, Mathison JC (1990) CD 14, a receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein. Science 249: 1431–3
Xu Y, Tao X, Shen B, Horng T, Medzhitov R, Manley JL, Tong L (2000) Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 408: 111–5
Xu Z, Dziarski R, Wang Q, Swartz K, Sakamoto KM, Gupta D (2001) Bacterial peptidoglycan-induced tnf-alpha transcription is mediated through the transcription factors Egr-1, Elk-1, and NF-KB. J Immunol 167: 6975–82
Yang RB, Mark MR, Gray A, Huang A, Xie MH, Zhang M, Goddard A, Wood WI, Gurney AL, Godowski PJ (1998) Toll-like receptor-2 mediates lipopolysaccharide-induced cellular signalling. Nature 395: 284–8
Yoshimura A, Lien E, Ingalls RR, Tuomanen E, Dziarski R, Golenbock D (1999) Cutting edge: recognition of gram-positive bacterial cell wall components by the innate immune system occurs via toll-like receptor 2. J Immunol 163: 1–5
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2002 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Kirschning, C.J., Schumann, R.R. (2002). TLR2: Cellular Sensor for Microbial and Endogenous Molecular Patterns. In: Beutler, B., Wagner, H. (eds) Toll-Like Receptor Family Members and Their Ligands. Current Topics in Microbiology and Immunology, vol 270. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59430-4_8
Download citation
DOI: https://doi.org/10.1007/978-3-642-59430-4_8
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-63975-3
Online ISBN: 978-3-642-59430-4
eBook Packages: Springer Book Archive