Differential activation of astrocytes by innate and adaptive immune stimuli
Differential activation of astrocytes by innate and adaptive immune stimuli
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DOI：
10.1002/glia.20117
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发表时间：
2005-02-01
期刊：
影响因子：
6.2
通讯作者：
Miller, SD
中科院分区：
文献类型：
--
作者：
Carpentier, PA;Begolka, WS;Miller, SD
中枢神经系统（CNS）的免疫豁免特性使得CNS驻留细胞能够对感染迅速作出反应至关重要。据报道，星形胶质细胞表达Toll样受体（TLRs），这是先天免疫系统的标志性模式识别受体，并会因受体结合而产生细胞因子作为应答。也有报道称星形胶质细胞会对适应性免疫系统的细胞因子作出反应，诱导产生抗原呈递功能。在此我们比较了TLR刺激物以及适应性免疫细胞因子干扰素 -γ（IFN -γ）和肿瘤坏死因子 -α（TNF -α）诱导星形胶质细胞多种免疫功能的能力。我们发现，与细胞因子刺激的星形胶质细胞相比，先天性信号脂多糖（LPS）和聚肌苷酸 - 聚胞苷酸（poly I:C）能更强地上调TLRs，产生细胞因子白细胞介素 - 6（IL - 6）和TNF -α，以及先天免疫效应分子干扰素 -α4、干扰素 -β和诱导型一氧化氮合酶（iNOS）。先天性刺激和适应性刺激都会诱导趋化因子CCL2、CCL3和CCL5产生相似的表达，也会使星形胶质细胞的黏附分子细胞间黏附分子 - 1（ICAM - 1）和血管细胞黏附分子 - 1（VCAM - 1）表达有相似的增强。然而，适应性免疫细胞因子的刺激在诱导主要组织相容性复合体II（MHC II）上调以及使星形胶质细胞具有激活CD4⁺T细胞的功能能力方面具有独特性。这些结果表明在中枢神经系统感染进展过程中，星形胶质细胞可能具有重要且不断变化的作用。（C）2004威利 - 利斯公司
The immunologic privilege of the central nervous system (CNS) makes it crucial that CNS resident cells be capable of responding rapidly to infection. Astrocytes have been reported to express Toll-like receptors (TLRs), hallmark pattern recognition receptors of the innate immune system, and respond to their ligation with cytokine production. Astrocytes have also been reported to respond to cytokines of the adaptive immune system with the induction of antigen presentation functions. Here we have compared the ability of TLR stimuli and the adaptive immune cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) to induce a variety of immunologic functions of astrocytes. We show that innate signals LPS- and poly I:C lead to stronger upregulation of TLRs and production of the cytokines IL-6 and TNF-a as well as innate immune effector molecules IFN-alpha4, IFN-beta, and iNOS compared with cytokine-stimulated astrocytes. Both innate stimulation and adaptive stimulation induce similar expression of the chemokines CCL2, CCL3, and CCL5, as well as similar enhancement of adhesion molecule ICAM-1 and VCAM-1 expression by astrocytes. Stimulation with adaptive immune cytokines, however, was unique in its ability to induce upregulation of MHC II and the functional ability of astrocytes to activate CD4(+) T cells. These results indicate potentially important and changing roles for astrocytes during the progression of CNS infection. (C) 2004 Wiley-Liss, Inc.