Drennan Michael B, Stijlemans Benoît, Van den Abbeele Jan, Quesniaux Valerie J, Barkhuizen Mark, Brombacher Frank, De Baetselier Patrick, Ryffel Bernhard, Magez Stefan
Immunology of Infectious Disease Medical Research Council/University of Cape Town Unit, Institute of Infectious Disease and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa.
J Immunol. 2005 Aug 15;175(4):2501-9. doi: 10.4049/jimmunol.175.4.2501.
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.
宿主对细胞外寄生虫布氏锥虫的初始反应的特征是早期释放与1型免疫反应相关的炎症介质。在本研究中，我们表明这种炎症反应依赖于接头分子MyD88介导的先天免疫系统的激活。在本研究中，MyD88缺陷型巨噬细胞对可溶性变异特异性表面糖蛋白（VSG）以及从布氏锥虫纯化的膜结合VSG均无反应。用布氏锥虫的克隆或非克隆株感染MyD88缺陷型小鼠会导致寄生虫血症水平升高。这伴随着感染初期血浆IFN-γ和TNF水平降低，随后在感染慢性期VSG特异性IgG2a抗体滴度适度降低。对几只TLR缺陷型小鼠的分析显示，在布氏锥虫感染期间，TLR9对IFN-γ的产生和VSG特异性IgG2a抗体水平有部分需求。这些结果表明哺乳动物TLR家族和MyD88信号传导参与了布氏锥虫的先天免疫识别。
