Allergens and microbial antigens impact on effector cells and antigen-presenting cells in allergic diseases. Allergens bind specifically to immunoglobulin E (IgE) linked to the high-affinity receptor for IgE (FcεRI) and stimulate a cascade of cellular events. This leads to the release of mediators of allergic reactions by effector cells on the one hand and antigen uptake, presentation and T cell priming by antigen-presenting cells on the other hand. In contrast, microbial antigens are recognized by pattern-recognition receptors (PRRs) of the innate immune system, to which Toll-like receptors (TLRs) belong. In view of the high number of microbial antigens, allergens and other soluble ligands in the cellular microenvironment in vivo, it is very likely that not only separate, but also concomitant stimulation of both receptor types, i.e. FcεRI and TLRs, occurs frequently under physiological conditions and in particular in the context of allergic and infectious disorders. Thus, interaction of TLRs with FcεRI and regulation of the IgE synthesis is of critical immunological importance, since it might profoundly modify the activation state of cells and the nature of the evolving immune responses. Current knowledge about the cross talk of TLRs with FcεRI- and IgE-related immune responses is discussed herein.

1.
Kraft S, Kinet JP: New developments in FcepsilonRI regulation, function and inhibition. Nat Rev Immunol 2007;7:365–378.
2.
Lin S, Cicala C, Scharenberg AM, Kinet JP: The Fc(epsilon)RIbeta subunit functions as an amplifier of Fc(epsilon)RIgamma-mediated cell activation signals. Cell 1996;85:985–995.
3.
Jin MS, Lee JO: Structures of the toll-like receptor family and its ligand complexes. Immunity 2008;29:182–191.
4.
Akira S, Takeda K: Toll-like receptor signalling. Nat Rev Immunol 2004;4:499–511.
5.
Iwasaki A, Medzhitov R: Toll-like receptor control of the adaptive immune responses. Nat Immunol 2004;5:987–995.
6.
Agrawal S, Kandimalla ER: Synthetic agonists of Toll-like receptors 7, 8 and 9. Biochem Soc Trans 2007;35:1461–1467.
7.
Jin MS, Lee JO: Structures of TLR-ligand complexes. Curr Opin Immunol 2008;20:414–419.
8.
Krieg AM: Therapeutic potential of Toll-like receptor 9 activation. Nat Rev Drug Discov 2006;5:471–484.
9.
Fitzgerald KA, Chen ZJ: Sorting out Toll signals. Cell 2006;125:834–836.
10.
O’Neill LA, Bowie AG: The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol 2007;7:353–364.
11.
Kraft S, Novak N: Fc receptors as determinants of allergic reactions. Trends Immunol 2006;27:88–95.
12.
Baumruker T, Csonga R, Jaksche D, Novotny V, Prieschl EE: TNF-alpha and IL-5 gene induction in IgE plus antigen-stimulated mast cells require common and distinct signaling pathways. Int Arch Allergy Immunol 1999;118:108–111.
13.
Okayama Y, Kawakami T: Development, migration, and survival of mast cells. Immunol Res 2006;34:97–115.
14.
Supajatura V, Ushio H, Nakao A, Akira S, Okumura K, Ra C, et al: Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. J Clin Invest 2002;109:1351–1359.
15.
McCurdy JD, Olynych TJ, Maher LH, Marshall JS: Cutting edge: distinct Toll-like receptor 2 activators selectively induce different classes of mediator production from human mast cells. J Immunol 2003;170:1625–1629.
16.
Kulka M, Metcalfe DD: TLR3 activation inhibits human mast cell attachment to fibronectin and vitronectin. Mol Immunol 2006;43:1579–1586.
17.
Matsushima H, Yamada N, Matsue H, Shimada S: TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells. J Immunol 2004;173:531–541.
18.
Yoshioka M, Fukuishi N, Iriguchi S, Ohsaki K, Yamanobe H, Inukai A, et al: Lipoteichoic acid downregulates FcepsilonRI expression on human mast cells through Toll-like receptor 2. J Allergy Clin Immunol 2007;120:452–461.
19.
Fehrenbach K, Port F, Grochowy G, Kalis C, Bessler W, Galanos C, et al: Stimulation of mast cells via FcvarepsilonR1 and TLR2: the type of ligand determines the outcome. Mol Immunol 2007;44:2087–2094.
20.
Qiao H, Andrade MV, Lisboa FA, Morgan K, Beaven MA: FcepsilonR1 and toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells. Blood 2006;107:610–618.
21.
Masuda A, Yoshikai Y, Aiba K, Matsuguchi T: Th2 cytokine production from mast cells is directly induced by lipopolysaccharide and distinctly regulated by c-Jun N-terminal kinase and p38 pathways. J Immunol 2002;169:3801–3810.
22.
Nigo YI, Yamashita M, Hirahara K, Shinnakasu R, Inami M, Kimura M, et al: Regulation of allergic airway inflammation through Toll-like receptor 4-mediated modification of mast cell function. Proc Natl Acad Sci USA 2006;103:2286–2291.
23.
Melendez AJ, Harnett MM, Pushparaj PN, Wong WS, Tay HK, McSharry CP, et al: Inhibition of Fc epsilon RI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes. Nat Med 2007;13:1375–1381.
24.
Selander C, Engblom C, Nilsson G, Scheynius A, Andersson CL: TLR2/MyD88-dependent and -independent activation of mast cell IgE responses by the skin commensal yeast Malassezia sympodialis. J Immunol 2009;182:4208–4216.
25.
Gilliet M, Cao W, Liu YJ: Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat Rev Immunol 2008;8:594–606.
26.
Sakurai D, Yamasaki S, Arase K, Park SY, Arase H, Konno A, et al: Fc epsilon RI gamma-ITAM is differentially required for mast cell function in vivo. J Immunol 2004;172:2374–2381.
27.
Novak N, Allam JP, Hagemann T, Jenneck C, Laffer S, Valenta R, et al: Characterization of FcepsilonRI-bearing CD123 blood dendritic cell antigen-2 plasmacytoid dendritic cells in atopic dermatitis. J Allergy Clin Immunol 2004;114:364–370.
28.
Foster B, Metcalfe DD, Prussin C: Human dendritic cell 1 and dendritic cell 2 subsets express FcepsilonRI: correlation with serum IgE and allergic asthma. J Allergy Clin Immunol 2003;112:1132–1138.
29.
Tversky JR, Le TV, Bieneman AP, Chichester KL, Hamilton RG, Schroeder JT: Human blood dendritic cells from allergic subjects have impaired capacity to produce interferon-alpha via Toll-like receptor 9. Clin Exp Allergy 2008;38:781–788.
30.
Schroeder JT, Bieneman AP, Xiao H, Chichester KL, Vasagar K, Saini S, et al: TLR9- and FcepsilonRI-mediated responses oppose one another in plasmacytoid dendritic cells by down-regulating receptor expression. J Immunol 2005;175:5724–5731.
31.
Schroeder JT, Chichester KL, Bieneman AP: Toll-like receptor 9 suppression in plasmacytoid dendritic cells after IgE-dependent activation is mediated by autocrine TNF-alpha. J Allergy Clin Immunol 2008;121:486–491.
32.
Cao W, Zhang L, Rosen DB, Bover L, Watanabe G, Bao M, et al: BDCA2/Fc epsilon RI gamma complex signals through a novel BCR-like pathway in human plasmacytoid dendritic cells. PLoS Biol 2007;5:e248.
33.
Cao W, Rosen DB, Ito T, Bover L, Bao M, Watanabe G, et al: Plasmacytoid dendritic cell-specific receptor ILT7-Fc epsilonRI gamma inhibits Toll-like receptor-induced interferon production. J Exp Med 2006;203:1399–1405.
34.
Le T, Tversky J, Chichester KL, Bieneman AP, Huang SK, Wood RA, et al: Interferons modulate FcepsilonRI-dependent production of autoregulatory IL-10 by circulating human monocytoid dendritic cells. J Allergy Clin Immunol 2009;123:217–233.
35.
Bussmann C, Peng WM, Bieber T, Novak N: Molecular pathogenesis and clinical implications of eczema herpeticum. Expert Rev Mol Med 2008;10:e21.
36.
Wollenberg A, Zoch C, Wetzel S, Plewig G, Przybilla B: Predisposing factors and clinical features of eczema herpeticum: a retrospective analysis of 100 cases. J Am Acad Dermatol 2003;49:198–205.
37.
Rajewsky K: Clonal selection and learning in the antibody system. Nature 1996;381:751–758.
38.
Bernasconi NL, Onai N, Lanzavecchia A: A role for Toll-like receptors in acquired immunity: up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells. Blood 2003;101:4500–4504.
39.
Bourke E, Bosisio D, Golay J, Polentarutti N, Mantovani A: The toll-like receptor repertoire of human B lymphocytes: inducible and selective expression of TLR9 and TLR10 in normal and transformed cells. Blood 2003;102:956–963.
40.
Ruprecht CR, Lanzavecchia A: Toll-like receptor stimulation as a third signal required for activation of human naive B cells. Eur J Immunol 2006;36:810–816.
41.
Liu N, Ohnishi N, Ni L, Akira S, Bacon KB: CpG directly induces T-bet expression and inhibits IgG1 and IgE switching in B cells. Nat Immunol 2003;4:687–693.
42.
He B, Qiao X, Cerutti A: CpG DNA induces IgG class switch DNA recombination by activating human B cells through an innate pathway that requires TLR9 and cooperates with IL-10. J Immunol 2004;173:4479–4491.
43.
Prud’homme GJ: Pathobiology of transforming growth factor beta in cancer, fibrosis and immunologic disease, and therapeutic considerations. Lab Invest 2007;87:1077–1091.
44.
Meiler F, Klunker S, Zimmermann M, Akdis CA, Akdis M: Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors. Allergy 2008;63:1455–1463.
45.
Feleszko W, Jaworska J, Hamelmann E: Toll-like receptors – novel targets in allergic airway disease (probiotics, friends and relatives). Eur J Pharmacol 2006;533:308–318.
46.
Marshall JD, Abtahi S, Eiden JJ, Tuck S, Milley R, Haycock F, et al: Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes T(H)1 cytokine expression while downregulating T(H)2 cytokine expression in PBMCs from human patients with ragweed allergy. J Allergy Clin Immunol 2001;108:191–197.
47.
Creticos PS, Schroeder JT, Hamilton RG, Balcer-Whaley SL, Khattignavong AP, Lindblad R, et al: Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N Engl J Med 2006;355:1445–1455.
48.
Wheeler AW, Marshall JS, Ulrich JT: A Th1-inducing adjuvant, MPL, enhances antibody profiles in experimental animals suggesting it has the potential to improve the efficacy of allergy vaccines. Int Arch Allergy Immunol 2001;126:135–139.
49.
Puggioni F, Durham SR, Francis JN: Monophosphoryl lipid A (MPL) promotes allergen-induced immune deviation in favour of Th1 responses. Allergy 2005;60:678–684.
50.
Allam JP, Peng WM, Appel T, Wenghoefer M, Niederhagen B, Bieber T, et al: Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells. J Allergy Clin Immunol 2008;121:368–374.
51.
Drachenberg KJ, Wheeler AW, Stuebner P, Horak F: A well-tolerated grass pollen-specific allergy vaccine containing a novel adjuvant, monophosphoryl lipid A, reduces allergic symptoms after only four preseasonal injections. Allergy 2001;56:498–505.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.