Abstract
Allergic reactions are dominated by the preferential development of specific Th2 responses against innocuous antigens in atopic individuals. This can reflect alterations in innate immune mechanisms. Toll-like receptors (TLRs) have evolved as key molecules., in innate and adaptive immunity. Their activation by structurally distinct exogenous or endogenous, ligands present at the cell microenvironment plays a critical role in antimicrobial defense. The global view is that TLR activation induces antigen-presenting, cells to produce cytokines that favor Th1-type immune responses, suggesting that it might prevent the development of deleterious Th2 responses in allergy. On the basis of epidemiological studies and recent data, it has been established that TLRs play a role in the development of Th2 responses. However, more information is needed to fully understand the mechanism of TLR involvement and the implication of immune cells that express TLRs in the Th1/Th2 cytokine profiles. Several TLRs, such as TLR9, TLR7, and TLR8, can be considered as good target candidates. Some TLR ligands, such as CpG DNA, are effective adjuvants, strong inducers of both IL-5 and eosinophilia downregulation. They are also potential links to allergen epitopes that could provide new allergen-specific immunotherapy regimens for the treatment of allergic disorders.
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Warner, J.O. (1999), Thorax 54(Suppl 2), S46-S51.
Platts-Mills, T.A., Woodfolk, J.A., and Sporik, R.B. (2001), Am J Reppir Crit Care Med 164, 1107–1108.
Von Mutius, E. (2001), Eur Respir J 18, 872–881.
Hakonarson, H. and Halapi, E. (2002), Am. J Pharmacogenomics 2, 155–166.
Vercelli, D., Baldini, M., Stern, D., Lohman, I.C., Halonen, M., and Martinez, F. (2001), J Endotoxin Res 7, 45–48.
Akira, S. (2003), Curr Opin Immunol 15, 5–11.
Kaisho, T. and Akira, S. (2002), Biochim. Biophys Acta 1589, 1–13.
Pham, T.Q., Goluszko P., Popov, V., Nowicki, S., and Nowicki, B.J. (1997), Infect Immun 65, 4309–4318.
Torsten, H., Schroeder, M.M., Lee, P.W., Yacono, C.L., Cannon, A.A., Gerçeker, D.E., et al. (2002), Proc Natl Acad Sci USA 99, 6907–6912.
Liu, Q.-H., Williams, D.A., McManus, C., Baribaud, F., Doms, R.W., Schols, D., et al. (2000), Proc Natl Acad Sci USA 97, 4832–4837.
Marshall, J.S., King, C.A., and McCurdy, J.D. (2003), Curr Pharm Des 9, 11–24.
Haziot, A., Hijiya, N., Gangloff, S.C., Silver, J., and Goyert, S.M. (2001), J Immunology 166, 1075–1078.
Haziot, A., Hijiya, N., Schultz, K., Zhang, F., Gangloff, S.C., and Goyert, S.M. (1999), J Immunology 162, 4801–4805.
Massari, P., Ram, S., Macleod, H., and Wetzler, L.M. (2003), Trends Microbiol 11, 87–93.
Takeuchi, O., Hoshino, K., and Akira., S. (2000), J Immunol 165, 5392–5396.
Kopp, E. and Medzhitov, R. (2003), Curr Opin Immunol 15, 396–401.
Alexopoulou, L., Holt, A.C., Medzhitov, R., Flavell, R.A. (2001), Nature 413, 732–738.
Takeuchi, O., Hoshino, K., Kawai, T., Sanjo, H., Takada, H., Ogawa, T., et al. (1999), Immunity 11, 443–451.
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., et al. (2000), Nature 408, 740–745.
Gangloff, S.C., Hijiya, N., Haziot, A., and Goyert, S.M. (1999), Clin Infect Dis 28, 491–496.
Michelsen, K.S., Aicher, A., Mohaupt, M., Hartung, T., Dimmeler, S., Kirschning, C.J., et al. (2001), J Biol Chem 276, 25,680–25,686.
Schwandner, R., Dziarski, R., Wesche, H., Rothe., M., and Kirschning, C.J. (1999), J Biol Chem 274, 17,406–17,409.
Kandimalla, E.R., Zhu, F.G., Bhagat, L., Yu, D., and Agrawal, S. (2003), Biochem Soc Trans 31, 654–658.
Hemmi, H., Kaisho, T., Takeuchi, O., Sato, S., Sanjo., H., Hoshino, K., et al. (2002), Nat Immunol 3, 196–200.
Jurk, M., Heil, F., Vollmer, J., Schetter, C., Krieg, A.M., Wagner, H. et al. (2002), Nat Immunol 3, 499.
Beg, A.A. (2002), Trends Immunol 23, 509–512.
Steinman, R.M. (1991), Annu Rev Immunol 9, 271–296.
Banchereau, J. and Steinman, R.M. (1998), Nature 392, 245–252.
Sozzani, S., Allavena, P., D'Amico., G., Luini, W., Bianchi, G., Kataura, M., et al. (1998), J Immunol 161, 1083–1086.
Dieu, M.C., Vanbervliet, B., Vicari, A., Bridon, J.M., Oldham, E., Ait-Yahia, S., et al. (1998), J Exp Med 188, 373–386.
De Smedt, T., Pajak, B., Muraille, E., Lespagnard, L., Heinen, E., De Baetselier, P., et al. (1996), J Exp Med 184, 1413–1424.
Dabbagh, K., Dahl, M.E., Stepick-Biek., P., and Lewis, D.B. (2002), J Immunol 168, 4524–4531.
Eisenbarth, S.C., Piggott,D.A., Huleatt, J.W., Visintin, I., Herrick, C.A., and Bottomly, K. (2002), J Exp Med 196, 1645–1651.
Muzio, M., Bosisio, D., Polentarutti, N., D'amico, G., Stoppacciaro., A., Mancinelli, R. et al. (2000), J Immunol 164, 5998–6004.
Zarember, K.A. and Godowski, P.J. (2002), J Immunol 168, 554–561.
Moser, M. and Murphy, K.M. (2000), Nat Immunol 1, 199–205.
Pulendran, B., Banchereau, J., Maraskovsky, E., and Maliszewski C. (2001), Trends Immunol 22, 41–47.
Romagnani, S. (2001), Curr Opin Allergy Clin Immunol 1, 73–78.
Guenounou, M. and David, B. (2000), Revue Française des laboratoires 328, 51–56.
Bacharier, L.B. and Geha, R.S. (2000), J Allergy Clin Immunol 105, S547-S548.
Beasley, R., Crane, J., Lai, C.K., and Pearce, N. (2000), J Allergy Clin Immunol 105, S466-S472.
Liu, A.H., Stanley, J., and Szefler, S.J., (2003), J Allergy Clin Immunol 111, S785-S792.
Lauener, R.P., Birchler, T., Adamski, J., Braun-Fahrlander, C., Bufe, A., Herz, U., et al.; ALEX study group. (2002), Lancet 360, 465–466.
Dabbagh, K. and Lewis, D.B. (2003), Curr Opin Infect Dis 16, 199–204.
Baldini, M., Lohman, I.C., Halonen, M., Erickson, R.P., Holt, P.G., and Martinez, F.D. (1999), Am J Respir Cell Mol Biol 20, 976–983.
Vercelli, D. (2002), J Allergy Clin Immunol 109, 14–21.
Lis, G., Kostyk, E., Sanak, M., and Pietrzyk, J.J. (2001), Pneumonol Alergol Pol 69, 265–272.
Schwartz, D.A. (2001), Respir Physiol 128, 47–55.
Schwartz, D.A., Thorne, P.S., Yagla, S.J., Burmeister, L.F., Olenchock, S.A., Watt, J.L., et al. (1995), Am J Respir Crit Care Med 152, 603–608.
Michel, O., Kips, J., Duchateau, J., Vertongen, F., Robert, L., Collet, H., et al. (1996), Am J Respir Crit Care Med 54, 1641–1646.
Arbour, N.C., Lorenz, E., Schutte., B.C., Zabner, J., Kline, J.N., Jones, M. et al. (2000), Nat Genet 25, 187–191.
Lapa e Silva, J.R., Possebon da Silva, M.D., Lefort, J., and Vargaftig, B.B. (2000), Toxicology 152, 31–35.
Masuda, A., Yoshikai, Y., Aiba, K., and Matsuguchi, T. (2002), J Immunol 169, 3801–3810.
Akira, S., Hoshino, K., and Kaisho, T. (2000), J Endotoxin Res 6, 383–387.
Schnare, M., Barton, G.M., Holt, A.C., Takeda, K., Akira, S., and Medzhitov, R. (2001), Nature Immunology 2, 947–950.
Von Hertzen, L.C. and Haahtela, T. (2000), Am J Respir Cell Mol Biol 22, 139–142.
Erb, K.J., Holloway, J.W., Sobeck, A., Moll, H., and Le Gros, G. (1998), J Exp Med 187, 561–569.
Supajatura, V., Ushio, H., Nakao, A., Akira, S., Okumura, K., Ra, C., et al. (2002), J Clin Invest 109, 1351–1359.
Varadaradjalou, S., Feger, F., Thieblemont, N., Hamouda, N.B., Pleau, J.M., Dy, M., et al. (2003), Eur J Immunol 33, 899–906.
Sparwasser, T., Miethke, T., Lipford, G., Erdmann, A., Hacker, H., Heeg, K., et al (1997), Eur J Immunol 27, 1671–1679.
Roman, M., Martin-Orozco, E., Goodman, J.S., Nguyen, M.D., Sato, Y., Ronaghy, A., et al. (1997), Nat Med 3, 849–854.
Wild, J.S. and Sur, S. (2001), Allergy 56, 365–376.
Krieg, A.M. (2002), Annu Rev Immunol 20, 709.
Kline, J.N., Krieg, A.M., Waldschmidt, T.J., Ballas, Z.K., Jain, V., and Businga, T.R. (1999), J Allergy Clin Immunol 104, 1258–1264.
Kitagaki, K., Jain, V.V., Businga, T.R., Hussain, I., and Kline, J.N. (2002), Clin Diagn Lab Immunol 9, 1260–1269.
Sur, S., Wild, J.S., Choudhury, B.K., Sur, N., Alam, R., and Klinman, D.M. (1999), J Immunol 162, 6284–6293.
Brugnolo, F., Sampognaro, S., Liotta, F., Cosmi, L., Annunziato, F., Manuelli, C., et al. (2003), J Allergy Clin Immunol 111, 380–388.
Ito, K., Amakawa, R., Kaisho, T., Hemmi, H., Tajima, K., Uehira., K., et al. (2002), J Exp Med 11, 1507–1512.
Broide, D., Schwarze, J., Tighe, H., Gifford, T., Nguyen, M.D., Malek, S., et al. (1998), J Immunol 161, 7054–7062.
Broide, D. and Sriramarao, P. (2001), Immunol Rev 179, 163–172.
Tighe, H., Takabayashi, K., Schwartz, D., Van Nest, G., Tuck, S., Eiden, J.J., et al. (2000), J Allergy Clin Immunol 106, 124–134.
Santeliz, J.V., Nest, G.V., Traquina, P., Larsen, E., and Wills-Karp, M. (2002), J Allergy Clin Immunol 109, 455–462.
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Gangloff, S.C., Guenounou, M. Toll-like receptors and immune response in allergic disease. Clinic Rev Allerg Immunol 26, 115–125 (2004). https://doi.org/10.1007/s12016-004-0006-0
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DOI: https://doi.org/10.1007/s12016-004-0006-0