TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lung.
TLR3 modulates immunopathology during a Schistosoma mansoni egg-driven Th2 response in the lung.
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DOI：
10.1002/eji.200838629
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发表时间：
2008-12
影响因子：
5.4
通讯作者：
Hogaboam CM
中科院分区：
文献类型：
--
作者：
Joshi AD;Schaller MA;Lukacs NW;Kunkel SL;Hogaboam CM
我们使用野生型 (TLR3+/+) 和 TLR3 基因缺陷 (TLR3−/−) 小鼠在曼氏沙门氏菌卵诱导的肺肉芽肿模型中研究了 Toll 样受体 3 (TLR3) 在 Th2 驱动的肺肉芽肿疾病中的作用。将曼氏沙门氏菌卵静脉推注至曼氏沙门氏菌致敏的 TLR3+/+ 小鼠中，与注射卵后第 8 天肺泡巨噬细胞以及离体脾脏和肺培养物中 TLR3 转录物表达的增加相关。与类似致敏和攻击的 TLR3+/+ 小鼠相比，TLR3−/− 小鼠的肺显示出肉芽肿大小增加、肉芽肿周围胶原沉积增多、Th2 细胞因子和趋化因子水平增加。 TLR3−/− 小鼠的巨噬细胞表现出 M2 表型，其特征是精氨酸酶和 CCL2 表达增加。卵子栓塞后第8天，与TLR3+/+小鼠相比，TLR3−/−小鼠肺部存在明显更多数量的CD4+CD25+T细胞。相对于 TLR3+/+ 细胞，来自 TLR3−/− 小鼠肉芽肿性肺和肺引流淋巴结的细胞释放出显着更高水平的 IL-17。因此，我们的数据表明，TLR3 在 Th2 驱动的肉芽肿反应中具有重要的调节作用，因为它的缺失增强了免疫病理学。
We examined the role of Toll Like Receptor 3 (TLR3) in Th2-driven pulmonary granulomatous disease, using wildtype (TLR3+/+) and TLR3 gene deficient (TLR3−/−) mice in a well-established model of S. mansoni egg induced pulmonary granuloma. The intravenous bolus injection of S. mansoni eggs into S. mansoni-sensitized TLR3+/+ mice was associated with an increase in TLR3 transcript expression in alveolar macrophages and ex vivo spleen and lung cultures at day 8 after egg injection. Lungs from TLR3−/− mice showed an increase in granuloma size, greater collagen deposition around the granuloma, and increased Th2 cytokine and chemokine levels compared with similarly sensitized and challenged TLR3+/+ mice. Macrophages from TLR3−/− mice exhibited a M2 phenotype characterized by increased arginase and CCL2 expression. Significantly greater numbers of CD4+CD25+ T cells were present in the lungs of TLR3−/− mice compared with TLR3+/+ mice at day 8 after egg embolization. Cells derived from granulomatous lung and lung draining lymph nodes of TLR3−/− mice released significantly higher levels of IL-17 levels relative to TLR3+/+ cells. Thus, our data suggest that TLR3 has a major regulatory role during a Th2-driven granulomatous response as its absence enhanced immunopathology.