Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy
Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy
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DOI：
10.4049/jimmunol.172.11.6978
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发表时间：
2004-06-01
影响因子：
4.4
通讯作者：
Nagler-Anderson, C
中科院分区：
文献类型：
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作者：
Bashir, MEH;Louie, S;Nagler-Anderson, C
先天免疫系统信号控制过敏易感性的机制还知之甚少。在这份报告中，我们发现，在三种不同品系的缺乏细菌脂多糖功能受体(Toll样受体4(TLR4))的小鼠中，灌胃给予带有粘膜佐剂的食物过敏原可诱导过敏原特异性IgE、血浆组胺水平升高和过敏症状，但在MHC匹配或同基因对照中不出现。在TLR4突变或缺陷小鼠的粘膜(肠系膜淋巴结和Peyer‘s补丁)和全身(脾)组织中，对过敏的敏感性与Th2偏向的细胞因子反应有关。TLR4突变小鼠调节Th1细胞因子产生的能力不会天生受损，因为它们通过TLR9对刺激做出反应。在TLR4突变小鼠与变态反应原加CT致敏期间联合给予CpG寡核苷酸可消除过敏症状和Ag特异性IgE，并导致Th1极化的细胞因子反应。当细菌菌群的组成被抗生素注射减少和改变时(从2周龄开始)，TLR4野生型小鼠与它们的TLR4突变小鼠一样容易受到过敏诱导的影响。在抗生素治疗的小鼠中，过敏原特异性的IgE和Th2细胞因子反应都减少了，在这些小鼠中，菌群已经被允许重新繁殖。综上所述，我们的结果表明，肠道共生菌提供的TLR4依赖的信号抑制了对食物AGS的过敏反应的发展。
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.