MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection
MyD88 is critical for the development of innate and adaptive immunity during acute lymphocytic choriomeningitis virus infection
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DOI：
10.1002/eji.200425730
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发表时间：
2005-03-01
影响因子：
5.4
通讯作者：
Finberg, RW
中科院分区：
文献类型：
--
作者：
Zhou, SH;Kurt-Jones, EA;Finberg, RW
我们研究了Toll样受体2(TLR2)和髓系分化因子88(MyD88)在淋巴细胞性脉络膜脑膜炎病毒(LCMV)感染过程中的作用，发现：(I)转基因细胞和小鼠腹腔巨噬细胞的研究表明，TLR2和MyD88对LCMV的初始促炎细胞因子应答(人IL-8、小鼠IL-6)是必需的；(Ii)TLR2基因敲除(KO)小鼠和MYD88 KO小鼠攻击LCMV后，血清中产生的IL-6和单核细胞趋化蛋白-1比野生型小鼠少；(Iii)与炎性细胞因子相反，LCMV诱导的1型干扰素(干扰素-α)的产生不依赖于MyD88；(Iv)MyD88在抗病毒CD8(+)T细胞反应中发挥重要作用，MyD88 KO小鼠的CD8(+)T细胞缺乏细胞内抗病毒细胞因子的表达；及(V)MyD88 KO小鼠未能激活CD8(+)T细胞伴随着MyD88 KO小鼠的持续病毒感染。我们证明TLR介导的应答在LCMV的先天性免疫应答中是重要的，MyD88对于控制LCMV感染和病毒特异性CD8(+)T细胞的成熟/激活是必不可少的。
We investigated the roles of Toll-like receptor 2 (TLR2) and myeloid differentiation factor 88 (MyD88) in the course of a lymphocytic choriomeningitis virus (LCMV) infection and revealed the following: (i) studies of transfected cells and murine peritoneal macrophages demonstrated that TLR2 and MyD88 are essential for the initial pro-inflammatory cytokine response (human IL-8, mouse IL-6) to LCMV; (ii) TLR2 knockout (KO) mice and MyD88 KO mice challenged with LCMV produced less IL-6 and monocyte chemotactic protein-1 in the serum than wild-type mice; (iii) in contrast to inflammatory cytokines, the production of type 1 IFN (IFN-alpha) in response to LCMV was MyD88 independent; (iv) MyD88 plays an essential role in antiviral CD8(+) T cell responses, CD8(+) T cells in MyD88 KO mice were defective in their expression of intracellular antiviral cytokines; and (v) the failure of MyD88 KO mice to activate CD8(+) T cells was accompanied by persistent viral infection in MyD88 KO mice. We demonstrate that TLR-mediated responses are important in the innate immune response to LCMV and that MyD88 is essential for the control of the LCMV infection and the maturation/activation of virus-specific CD8(+) T cells.