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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Herpes simplex virus type-1 induces IFN-{alpha} production via Toll-like receptor 9-dependent and -independent pathways.
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Herpes simplex virus type-1 induces IFN-{alpha} production via Toll-like receptor 9-dependent and -independent pathways.

机译：1型单纯疱疹病毒通过Toll样受体9依赖性和非依赖性途径诱导IFN-α的产生。

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摘要

Type I IFN production in response to the DNA virus herpes simplex virus type-1 (HSV-1) is essential in controlling viral replication. We investigated whether plasmacytoid dendritic cells (pDC) were the major tissue source of IFN-alpha, and whether the production of IFN-alpha in response to HSV-1 depended on Toll-like receptor 9 (TLR9). Total spleen cells or bone marrow (BM) cells, or fractions thereof, including highly purified pDC, from WT, TLR9, and MyD88 knockout mice were stimulated with known ligands for TLR9 or active HSV-1. pDC freshly isolated from both spleen and BM were the major source of IFN-alpha in response to oligodeoxynucleotides containing CpG motifs, but in response to HSV-1 the majority of IFN-alpha was produced by other cell types. Moreover, IFN-alpha production by non-pDC was independent of TLR9. The tissue source determined whether pDC responded to HSV-1 in a strictly TLR9-dependent fashion. Freshly isolated BM pDC or pDC derived from culture of BM precursors with FMS-like tyrosine kinase-3 ligand, produced IFN-alpha in the absence of functional TLR9, whereas spleen pDC did not. Heat treatment of HSV-1 abolished maturation and IFN-alpha production from all TLR9-deficient DC but not WT DC. Thus pDC and non-pDC produce IFN-alpha in response to HSV-1 via both TLR9-independent and -dependent pathways.
机译：响应DNA病毒单纯疱疹病毒1型（HSV-1）的I型IFN产生对于控制病毒复制至关重要。我们调查了浆细胞样树突状细胞（pDC）是否是IFN-α的主要组织来源，以及是否响应HSV-1产生IFN-α取决于Toll样受体9（TLR9）。用已知的TLR9配体或活性HSV-1刺激来自WT，TLR9和MyD88敲除小鼠的总脾细胞或骨髓（BM）细胞或其部分，包括高度纯化的pDC。从脾脏和BM新鲜分离出的pDC是IFN-α的主要来源，是对含有CpG基序的寡脱氧核苷酸的反应，但对HSV-1的反应，大多数IFN-α是由其他细胞类型产生的。此外，非pDC产生的IFN-α与TLR9无关。组织来源确定pDC是否严格以TLR9依赖性方式响应HSV-1。新鲜分离的BM pDC或源自具有FMS样酪氨酸激酶-3配体的BM前体培养物的pDC在缺乏功能性TLR9的情况下产生IFN-α，而脾pDC则不产生。 HSV-1的热处理消除了所有TLR9缺陷型DC而非WT DC的成熟和IFN-α的产生。因此，pDC和非pDC通过TLR9非依赖性和非依赖性途径对HSV-1产生IFN-α。

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