Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells
Virus or TLR agonists induce TRAIL-mediated cytotoxic activity of plasmacytoid dendritic cells
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DOI：
10.4049/jimmunol.176.1.248
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
Plumas, J
中科院分区：
文献类型：
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作者：
Chaperot, L;Blum, A;Plumas, J
在树突状细胞中，浆细胞样树突状细胞（PDC）代表了功能上不同的谱系。关于先天免疫，PDC 在病毒暴露或受到微生物产物（例如含有寡 DNA 的未甲基化 CpG 基序）刺激后，由于选择性表达 TLR7 和 TLR9，会分泌大量 I 型 IFN。我们询问它们是否可以在感染早期或用 TLR7 或 TLR9 激动剂激活后获得细胞毒功能。在本研究中，我们描述了一种名为 GEN2.2 的人类 PDC 细胞系，该细胞系源自白血病 PDC，具有正常 PDC 的大部分表型和功能特征。我们发现，在与流感病毒接触后，GEN2.2 以及正常的 PDC 获得 TRAIL 和针对 TRAIL 敏感靶细胞的杀伤活性。此外，我们发现含有寡聚DNA或R848的CpG基序对GEN2.2细胞的激活也会诱导TRAIL并赋予它们杀死黑色素瘤细胞的能力。因此，PDC可能代表先天免疫的主要组成部分，可以参与感染细胞和肿瘤细胞的清除。这种现象可能与 TLR7 或 TLR9 激动剂在传染病和癌症治疗中的功效有关。
Among dendritic cells, plasmacytoid dendritic cells (PDC) represent a functionally distinct lineage. Regarding innate immunity, PDC secrete large amounts of type I IFN upon viral exposure or stimulation by microbial products such as unmethylated CpG-motif containing oligo-DNA due to their selective expression of TLR7 and TLR9. We asked whether they could acquire cytotoxic functions during the early phases of infection or after activation with TLR7 or TLR9 agonists. In the present study, we describe a human PDC cell line called GEN2.2, derived from leukemic PDC, that shares most of the phenotypic and functional features of normal PDC. We show that after contact with the influenza virus, GEN2.2, as well as normal PDC, acquires TRAIL and killer activity against TRAIL-sensitive target cells. Moreover, we show that activation of GEN2.2 cells by CpG-motif containing oligo-DNA or R848 also induces TRAIL and endows them with the ability to kill melanoma cells. Therefore, PDC may represent a major component of innate immunity that could participate to the clearance of infected cells and tumor cells. This phenomenon could be relevant for the efficacy of TLR7 or TLR9 agonists in the therapy of infectious disease and cancer.