Mesenchymal stem cells detect and defend against gammaherpesvirus infection via the cGAS-STING pathway.
Mesenchymal stem cells detect and defend against gammaherpesvirus infection via the cGAS-STING pathway.
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间充质干细胞通过 cGAS-STING 途径检测并防御伽马疱疹病毒感染
DOI：
10.1038/srep07820
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发表时间：
2015-01-16
影响因子：
4.6
通讯作者：
Huang X
中科院分区：
文献类型：
--
作者：
Yang K;Wang J;Wu M;Li M;Wang Y;Huang X
间充质干细胞（MSCs）由于其多能性和免疫调节作用被广泛应用于临床治疗组织损伤和自身免疫性疾病。长期观察揭示了骨髓间充质干细胞输注后的一些并发症，特别是疱疹病毒感染。然而，MSCs中宿主防御疱疹病毒的机制在很大程度上仍然未知。在这里，我们发现小鼠γ疱疹病毒-68 （MHV-68）在遗传和生物学上与人类γ疱疹病毒相关，在体外和体内都能有效地感染间充质干细胞。细胞质DNA传感器环GMP-AMP合成酶（cGAS）首次被鉴定为MSCs中MHV-68的传感器。此外，胞质DNA感应途径通过接头STING和下游激酶TBK1介导了有效的抗疱疹病毒作用。此外，阻断IFN信号表明，胞质DNA感知触发了IFN依赖性和非依赖性抗疱疹病毒反应。我们的研究结果表明，cGAS-STING介导了间充质干细胞对γ疱疹病毒感染的先天免疫，这可能为制定治疗策略提供线索。
Mesenchymal stem cells (MSCs) are widely used in clinical settings to treat tissue injuries and autoimmune disorders due to their multipotentiality and immunomodulation. Long-term observations reveal several complications after MSCs infusion, especially herpesviral infection. However, the mechanism of host defense against herpesviruses in MSCs remains largely unknown. Here we showed that murine gammaherpesvirus-68 (MHV-68), which is genetically and biologically related to human gammaherpesviruses, efficiently infected MSCs bothin vitroandin vivo. Cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) was identified as the sensor of MHV-68 in MSCs for the first time. Moreover, the cytosolic DNA sensing pathway mediated a potent anti-herpesviral effect through the adaptor STING and downstream kinase TBK1. Furthermore, blockade of IFN signaling suggested that cytosolic DNA sensing triggered both IFN-dependent and -independent anti-herpesviral responses. Our findings demonstrate that cGAS-STING mediates innate immunity to gammaherpesvirus infection in MSCs, which may provide a clue to develop therapeutic strategy.
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影响因子：
3.7
作者：
Kim H;Lee W;Lee S
通讯作者：
Lee S
影响因子：
64.5
作者：
Dixit E;Boulant S;Zhang Y;Lee AS;Odendall C;Shum B;Hacohen N;Chen ZJ;Whelan SP;Fransen M;Nibert ML;Superti-Furga G;Kagan JC
通讯作者：
Kagan JC
DOI：
10.1111/j.1749-6632.2012.06667.x
发表时间：
2012-01-01
期刊：
HEMATOPOIETIC STEM CELLS VIII
影响因子：
--
作者：
Bernardo, Maria Ester;Fibbe, Willem E.
通讯作者：
Fibbe, Willem E.
影响因子：
4.3
作者：
Dulery, Remy;Salleron, Julia;Yakoub-Agha, Ibrahim
通讯作者：
Yakoub-Agha, Ibrahim
影响因子：
5.4
作者：
Gargano, Lisa M.;Forrest, J. Craig;Speck, Samuel H.
通讯作者：
Speck, Samuel H.