HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bashir, M. E. H. Articles by Nagler-Anderson, C. Search for Related Content PubMed PubMed Citation Articles by Bashir, M. E. H. Articles by Nagler-Anderson, C.

Toll-Like Receptor 4 Signaling by Intestinal Microbes Influences Susceptibility to Food Allergy¹

Mucosal Immunology Laboratory, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129

The mechanisms by which signaling by the innate immune system controls susceptibility to allergy are poorly understood. In this report, we show that intragastric administration of a food allergen with a mucosal adjuvant induces allergen-specific IgE, elevated plasma histamine levels, and anaphylactic symptoms in three different strains of mice lacking a functional receptor for bacterial LPS (Toll-like receptor 4 (TLR4)), but not in MHC-matched or congenic controls. Susceptibility to allergy correlates with a Th2-biased cytokine response in both the mucosal (mesenteric lymph node and Peyer’s patch) and systemic (spleen) tissues of TLR4-mutant or -deficient mice. TLR4-mutant mice are not inherently impaired in their ability to regulate Th1 cytokine production because they respond to stimulation via TLR9. Coadministration of CpG oligodeoxynucleotides during sensitization of TLR4-mutant mice with allergen plus CT abrogates anaphylactic symptoms and Ag-specific IgE, and results in a Th1-polarized cytokine response. When the composition of the bacterial flora is reduced and altered by antibiotic administration (beginning at 2 wk of age), TLR4 wild-type mice become as susceptible to the induction of allergy as their TLR4-mutant counterparts. Both allergen-specific IgE and Th2 cytokine responses are reduced in antibiotic-treated mice in which the flora has been allowed to repopulate. Taken together, our results suggest that TLR4-dependent signals provided by the intestinal commensal flora inhibit the development of allergic responses to food Ags.

This article has been cited by other articles:

				F. Capobianco, C. Butteroni, B. Barletta, S. Corinti, C. Afferni, R. Tinghino, M. Boirivant, and G. Di Felice Oral sensitization with shrimp tropomyosin induces in mice allergen-specific IgE, T cell response and systemic anaphylactic reactions Int. Immunol., June 18, 2008; (2008) dxn065v1. [Abstract] [Full Text] [PDF]

				A. Wald and D. Rakel Behavioral and Complementary Approaches for the Treatment of Irritable Bowel Syndrome Nutr Clin Pract, June 1, 2008; 23(3): 284 - 292. [Abstract] [Full Text] [PDF]

				M. R. Goldberg, O. Nadiv, N. Luknar-Gabor, G. Zadik-Mnuhin, J. Tovbin, and Y. Katz Correlation of Th1-Type Cytokine Expression and Induced Proliferation to Lipopolysaccharide Am. J. Respir. Cell Mol. Biol., June 1, 2008; 38(6): 733 - 737. [Abstract] [Full Text] [PDF]

				S. Nutten, A. Schumann, D. Donnicola, A. Mercenier, S. Rami, and C. L. Garcia-Rodenas Antibiotic Administration Early in Life Impairs Specific Humoral Responses to an Oral Antigen and Increases Intestinal Mast Cell Numbers and Mediator Concentrations Clin. Vaccine Immunol., February 1, 2007; 14(2): 190 - 197. [Abstract] [Full Text] [PDF]

				M. R. Goldberg, N. Luknar-Gabor, G. Zadik-Mnuhin, P. Koch, J. Tovbin, and Y. Katz Synergy between LPS and immobilized anti-human CD3{epsilon} mAb for activation of cord blood CD3+ T cells Int. Immunol., January 1, 2007; 19(1): 99 - 103. [Abstract] [Full Text] [PDF]

				E. CARIO and D. K PODOLSKY Toll-like receptor signaling and its relevance to intestinal inflammation. Ann. N.Y. Acad. Sci., August 1, 2006; 1072: 332 - 338. [Abstract] [Full Text] [PDF]

				M. N. Ince, D. E. Elliott, T. Setiawan, A. Blum, A. Metwali, Y. Wang, J. F. Urban Jr., and J. V. Weinstock Cutting Edge: Heligmosomoides polygyrus Induces TLR4 on Murine Mucosal T Cells That Produce TGF{beta} after Lipopolysaccharide Stimulation J. Immunol., January 15, 2006; 176(2): 726 - 729. [Abstract] [Full Text] [PDF]

				N. E. NIEUWENHUIZEN and A. L. LOPATA Fighting Food Allergy: Current Approaches Ann. N.Y. Acad. Sci., November 1, 2005; 1056(1): 30 - 45. [Abstract] [Full Text] [PDF]

				E Cario BACTERIAL INTERACTIONS WITH CELLS OF THE INTESTINAL MUCOSA: TOLL-LIKE RECEPTORS AND NOD2 Gut, August 1, 2005; 54(8): 1182 - 1193. [Full Text] [PDF]

				S. J. Rhee, W. A. Walker, and B. J. Cherayil Developmentally Regulated Intestinal Expression of IFN-{gamma} and Its Target Genes and the Age-Specific Response to Enteric Salmonella Infection J. Immunol., July 15, 2005; 175(2): 1127 - 1136. [Abstract] [Full Text] [PDF]

				M. T. Abreu, M. Fukata, and M. Arditi TLR Signaling in the Gut in Health and Disease J. Immunol., April 15, 2005; 174(8): 4453 - 4460. [Abstract] [Full Text] [PDF]

				D. W. Smith and C. Nagler-Anderson Preventing Intolerance: The Induction of Nonresponsiveness to Dietary and Microbial Antigens in the Intestinal Mucosa J. Immunol., April 1, 2005; 174(7): 3851 - 3857. [Abstract] [Full Text] [PDF]