Toll-like receptor 3 promotes cross-priming to virus-infected cells
Toll-like receptor 3 promotes cross-priming to virus-infected cells
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DOI：
10.1038/nature03326
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发表时间：
2005-02-24
期刊：
影响因子：
64.8
通讯作者：
Sousa, CRE
中科院分区：
文献类型：
--
作者：
Schulz, O;Diebold, SS;Sousa, CRE
细胞相关抗原的交叉呈递在调节CD8(+) T细胞对抗原呈递细胞（APCs）不表达的蛋白的应答中起重要作用(1)。树突状细胞是体内主要的交叉呈递apc，在阐明允许树突状细胞捕获和处理细胞物质的途径方面已经取得了很大进展(1)。然而，决定这种呈递最终是否导致细胞毒性T细胞（CTL）反应（交叉启动）或CD8(+) T细胞失活（交叉耐受）的信号知之甚少。在这里，我们描述了一种在病毒感染期间促进交叉引物的机制。我们发现小鼠CD8alpha（+）树突状细胞被双链RNA激活，双链RNA存在于病毒感染的细胞中，而不存在于未感染的细胞中。树突状细胞的激活需要吞噬被感染的物质，然后通过dsRNA受体toll样受体3 （TLR3）发出信号。用病毒感染的细胞或含有合成dsRNA的细胞免疫可导致针对细胞相关抗原的CTL交叉引物显著增加，这在很大程度上依赖于抗原呈递细胞的TLR3表达。因此，TLR3可能已经进化到允许交叉启动ctl来对抗不直接感染树突状细胞的病毒。
Cross-presentation of cell-associated antigens plays an important role in regulating CD8(+) T cell responses to proteins that are not expressed by antigen-presenting cells (APCs)(1). Dendritic cells are the principal cross-presenting APCs in vivo and much progress has been made in elucidating the pathways that allow dendritic cells to capture and process cellular material(1). However, little is known about the signals that determine whether such presentation ultimately results in a cytotoxic T cell (CTL) response (cross-priming) or in CD8(+) T cell inactivation (cross-tolerance). Here we describe a mechanism that promotes cross-priming during viral infections. We show that murine CD8alpha(+) dendritic cells are activated by double-stranded (ds)RNA present in virally infected cells but absent from uninfected cells. Dendritic cell activation requires phagocytosis of infected material, followed by signalling through the dsRNA receptor, toll-like receptor 3 (TLR3). Immunization with virus-infected cells or cells containing synthetic dsRNA leads to a striking increase in CTL cross-priming against cell-associated antigens, which is largely dependent on TLR3 expression by antigen-presenting cells. Thus, TLR3 may have evolved to permit cross-priming of CTLs against viruses that do not directly infect dendritic cells.