Toll-Like Receptor 4 Signaling by Intestinal Microbes Influences Susceptibility to Food Allergy
| Autor: | Mohamed Elfatih H. Bashir, Steve Louie, Hai Ning Shi, Cathryn Nagler-Anderson |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Allergy
Arachis CpG Oligodeoxynucleotide Immunology Mice Inbred Strains Receptors Cell Surface Immunoglobulin E Mice Th2 Cells Food allergy medicine Animals Immunology and Allergy Mice Knockout Toll-like receptor Membrane Glycoproteins Innate immune system biology Toll-Like Receptors TLR9 medicine.disease Anti-Bacterial Agents DNA-Binding Proteins Intestines Toll-Like Receptor 4 Toll-Like Receptor 9 biology.protein TLR4 Female Disease Susceptibility Food Hypersensitivity Signal Transduction |
| Zdroj: | The Journal of Immunology. 172:6978-6987 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.172.11.6978 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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