House dust extracts elicit Toll-like receptor-dependent dendritic cell responses
House dust extracts elicit Toll-like receptor-dependent dendritic cell responses
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DOI：
10.1016/j.jaci.2005.03.015
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发表时间：
2005-07-01
影响因子：
14.2
通讯作者：
Horner, AA
中科院分区：
文献类型：
--
作者：
Boasen, J;Chisholm, D;Horner, AA
背景：实验室和流行病学研究提供了间接但令人信服的证据，表明 Toll 样受体 (TLR) 在宿主对环境免疫刺激因素的先天反应中发挥着重要作用。然而，直接证据很少。目的：确定房屋灰尘提取物是否通过 TLR 依赖性机制激活树突状细胞。方法：在初步研究中，用无菌房屋灰尘提取物培养骨髓来源的树突状细胞，并评估细胞因子的产生和共刺激分子的表达。在其他实验中，评估了这些反应的 TLR 依赖性。 结果：发现屋尘提取物激活的骨髓源性树突状细胞以浓度依赖性方式产生 IL-6 和 IL-12，并增加其 CD40、CD80、CD86 和 MHC II 类分子的表达。此外，室内灰尘提取物的相对生物活性与其内毒素水平之间存在相关性。最后，来自 TLR（2、49 和 9）缺陷小鼠的骨髓来源的树突细胞均表现出反应减弱，而 MyD88 缺陷的骨髓来源的树突细胞几乎对室内灰尘提取物完全没有反应。结论：这些研究提供了直接证据，表明 TLR 信号通路在至少一部分树突细胞对生活环境中普遍存在的非感染性因素的反应中发挥着核心作用。
Background: Laboratory and epidemiological studies have provided indirect but compelling evidence that Toll-like receptors (TLRs) play an important role in innate host responsiveness to ambient immunostimulatory factors. However, little direct evidence exists.Objective: To determine whether house dust extracts activate dendritic cells by TLR-dependent mechanisms.Methods: In initial studies, bone marrow-derived dendritic cells were cultured with sterile house dust extracts, and cytokine production and costimulatory molecule expression were evaluated. In additional experiments, the TLR dependence of these responses was assessed.Results: House dust extract-activated bone marrow-derived dendritic cells were found to produce IL-6 and IL-12 in a concentration-dependent manner and to increase their expression of CD40, CD80, CD86, and MHC class II molecules. Furthermore, correlations were seen between the relative bioactivities of house dust extracts and their endotoxin levels. Finally, bone marrow-derived dendritic cells from TLR (2, 49 and 9)-deficient mice all demonstrated attenuated responses, and MyD88 deficient bone marrow-derived dendritic cells were almost completely nonresponsive to house dust extracts.Conclusion: These investigations provide direct evidence that TLR signaling pathways play a central role in at least a subset of dendritic cell responses to noninfectious factors ubiquitous in living environments.