TLR4 signaling attenuates ongoing allergic inflammation
TLR4 signaling attenuates ongoing allergic inflammation
复制标题
DOI：
10.4049/jimmunol.176.10.5856
复制
发表时间：
2006-05-15
影响因子：
4.4
通讯作者：
Cook, Donald N.
中科院分区：
文献类型：
--
作者：
Hollingsworth, John W.;Whitehead, Gregory S.;Cook, Donald N.
LPS暴露和过敏性哮喘之间的关系知之甚少。人类流行病学研究发现，暴露于LPS可以保护、没有影响或加重过敏性哮喘。类似地，LPS对小鼠中的过敏性肺部炎症具有可变的影响，这取决于所使用的模型。在本研究中，我们研究了非常低剂量的LPS在短期和长期过敏原攻击模型中的作用。当用过敏原短时间攻击时，野生型和tlr 4缺陷型小鼠有相似的反应。然而，当挑战1周或更长的时间，tlr 4缺陷小鼠气道嗜酸性粒细胞，血清IgE和Th 2细胞因子显着增加相比，类似的挑战，遗传匹配的C57 BL/6小鼠。在C57 BL/6小鼠中观察到的过敏反应的相对减弱依赖于骨髓来源的细胞特异性表达trl 4，并且与Th 1反应的增加无关。与C57 BL/6小鼠相比，tlr 4基因缺陷小鼠肺组织中树突状细胞的数量显著增加。在暴露于类似的OVA制剂后，未处理过的C57 BL/6和tlr 4缺陷小鼠产生过敏原特异性耐受的能力没有差异，这表明现有炎症的耐受和调节通过不同的机制产生。当这些小鼠用补充有额外LPS的OVA攻击时，C57 BL/6小鼠中嗜酸性粒细胞炎症的减弱被消除。总之，这些发现表明，低剂量的内毒素可以对过敏性炎症产生调节作用，特别是在持续暴露于过敏原的情况下。
The relationship between LPS exposure and allergic asthma is poorly understood. Epidemiologic studies in humans have found that exposure to LPS can protect, have no effect, or exacerbate allergic asthma. Similarly, LPS has had variable effects on allergic pulmonary inflammation in the mouse, depending on the model used. In the present study, we studied the effect of very low doses of LPS in models of both short-term and long-term allergen challenge. When challenged with allergen for short periods, wild-type and tlr4-deficient mice had similar responses. However, when challenged for periods of 1 wk or longer, tlr4-deficient mice developed dramatically increased airway eosinophils, serum IgE, and Th2 cytokines compared with similarly challenged, genetically matched C57BL/6 mice. The relative attenuation of allergic responses seen in C57BL/6 mice was dependent on bone marrow-derived cell-specific expression of trl4, and was not associated with an increase in Th1 responses. The number of dendritic cells in lungs of challenged tlr4-deficient mice was significantly increased compared with those in challenged C57BL/6 mice. No differences were seen in the abilities of naive C57BL/6 and tlr4-deficient mice to develop allergen-specific tolerance after exposure to similar preparations of OVA, suggesting that tolerance and regulation of existing inflammation develop through different mechanisms. The attenuation of eosinophilic inflammation in C57BL/6 mice was abolished when these mice were challenged with OVA supplemented with additional LPS. Together, these findings show that low doses of endotoxin can have regulatory effects on allergic inflammation, particularly in the setting of ongoing allergen exposure.