The induction of a type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent
The induction of a type 1 immune response following a Trypanosoma brucei infection is MyD88 dependent
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DOI：
10.4049/jimmunol.175.4.2501
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发表时间：
2005-08-15
影响因子：
4.4
通讯作者：
Magez, S
中科院分区：
文献类型：
--
作者：
Drennan, MB;Stijlemans, B;Magez, S
宿主对胞外寄生虫布鲁氏锥虫的最初反应是早期释放与1型免疫反应相关的炎性介质。在这项研究中，我们证明这种炎症反应依赖于适配器分子MyD88介导的天然免疫系统的激活。在目前的研究中，MyD88缺陷的巨噬细胞对可溶性变体特异性表面糖蛋白(VSG)以及从布氏毛滴虫中纯化的膜结合VSG都没有反应。用克隆或非克隆的布氏毛滴虫感染MyD88缺陷小鼠，可导致寄生虫血症水平升高。伴随而来的是感染初期血浆中干扰素-γ和肿瘤坏死因子水平的降低，以及慢性感染阶段VSG特异性IgG2a抗体效价的适度降低。对几只TLR缺陷小鼠的分析表明，在布氏毛滴虫感染期间，TLR9在产生干扰素-γ和VSG特异性IgG2a抗体水平方面是部分需要的。这些结果表明哺乳动物的TLR家族和MyD88信号转导通路参与了布鲁氏毛滴虫的天然免疫识别。
The initial host response toward the extracellular parasite Trypanosoma brucei is characterized by the early release of inflammatory mediators associated with a type 1 immune response. In this study, we show that this inflammatory response is dependent on activation of the innate immune system mediated by the adaptor molecule MyD88. In the present study, MyD88-deficient macrophages are nonresponsive toward both soluble variant-specific surface glycoprotein (VSG), as well as membrane-bound VSG purified from T. brucei. Infection of MyD88-deficient mice with either clonal or nonclonal stocks of T. brucei resulted in elevated levels of parasitemia. This was accompanied by reduced plasma IFN-gamma and TNF levels during the initial stage of infection, followed by moderately lower VSG-specific IgG2a Ab titers during the chronic stages of infection. Analysis of several TLR-deficient mice revealed a partial requirement for TLR9 in the production of IFN-gamma and VSG-specific IgG2a Ab levels during T. brucei infections. These results implicate the mammalian TLR family and MyD88 signaling in the innate immune recognition of T. brucei.