Toll-like receptor 4 or 2 agonists decrease allergic inflammation
Toll-like receptor 4 or 2 agonists decrease allergic inflammation
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DOI：
10.1165/rcmb.2003-0435oc
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发表时间：
2005-03-01
影响因子：
6.4
通讯作者：
Finn, PW
中科院分区：
文献类型：
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作者：
Velasco, G;Campo, M;Finn, PW
Toll样受体（TLR）识别高度保守的微生物分子模式，例如在内毒素中发现的。本研究测试了体内TLR 4和TLR 2刺激是否会调节随后的适应性（过敏性）免疫应答。我们分析了肺给药的TLR 4激动剂，脂质A（LPA），和两个TLR 2激动剂，肽聚糖（Ppg）和PamCys，在小鼠过敏性炎症模型的影响。TLR激动剂在过敏原致敏或激发期间施用。两种TLR激动剂在致敏或激发时均可降低过敏原诱导的嗜酸性粒细胞肺募集。当在致敏前给药时，TLR 4和TLR 2激动剂降低了过敏原诱导的炎症参数（肺嗜酸性粒细胞增多症、支气管肺泡灌洗液IL-13、总血清IgE和气道高反应性）。有趣的是，TLR 4和TLR 2激动剂减少了肺中CD 4+细胞的数量。此外，在局部过敏原刺激的部位，引流胸淋巴结，过敏原诱导的淋巴细胞增殖和IL-13分泌减少，通过给药LpA和Ppg。这些数据提供了非抗原依赖性刺激调节适应性（过敏性）反应的独特实例。我们的研究结果还表明，TLR 4和TLR 2激动剂都能降低过敏反应，这支持了在特定条件下暴露于细菌组分可以预防过敏性疾病的概念。
Toll-like receptors (TLRs) recognize highly conserved microbial molecular patterns, such as found in endotoxin. This study tested whether TLR4 and TLR2 stimulation in vivo would modulate subsequent adaptive (allergic) immune responses. We analyzed the effects of pulmonary administration of a TLR4 agonist, lipid A (LpA), and two TLR2 agonists, peptidoglycan (Ppg) and PamCys, in a murine model of allergic inflammation. The TLR agonists were administered during allergen sensitization or challenge. Both TLR agonists decreased the allergen-induced pulmonary recruitment of eosinophils when administered at sensitization or challenge. When given before sensitization, the TLR4 and TLR2 agonists decreased additional allergen-induced parameters of inflammation (pulmonary eosinophilia, bronchoalveolar lavage IL-13, total serum IgE, and airway hyperresponsiveness). Interestingly, TLR4 and TLR2 agonists decreased the number of CD4+ cells in the lung. Also, at the site of local allergen stimulation, the draining thoracic lymph nodes, allergen-induced lymphocyte proliferation, and IL-13 secretion were decreased by administration of LpA and Ppg. These data provide a distinct example of the modulation of adaptive (allergic) responses by non-antigen-dependent stimuli. Our findings also demonstrate that both TLR4 and TLR2 agonists decrease allergic responses, supporting the concept that exposure to bacterial components under defined conditions may protect against allergic disease.