Innate immune DNA sensing pathways: STING, AIMII and the regulation of interferon production and inflammatory responses.
Innate immune DNA sensing pathways: STING, AIMII and the regulation of interferon production and inflammatory responses.
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DOI：
10.1016/j.coi.2010.12.015
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发表时间：
2011-02
影响因子：
7
通讯作者：
Barber GN
中科院分区：
文献类型：
--
作者：
Barber GN
微生物的早期检测是先天免疫系统的责任，先天免疫系统已经进化为感知病原体衍生的分子如脂多糖和非自身核酸，以触发宿主防御对策。这些传感器包括特异性识别病毒RNA的RIG-I样解旋酶家族（RLH），以及感测多种微生物衍生分子的细胞质、核苷酸结合寡聚化结构域（NOD）样受体和Toll样受体（TLR）途径。理解细胞如何感知由某些病毒，细菌和可能的寄生虫产生的外来DNA已被证明是难以捉摸的，但具有重要意义，因为这些信息可以深入了解微生物相关疾病的原因，包括病毒相关癌症和自身免疫性疾病。已知浆细胞样树突状细胞利用TLR 9来检测病原体相关DNA并触发I型干扰素（IFN）以及其他细胞因子的产生，尽管替代的关键DNA检测传感器仍有待鉴定。然而，最近发现一种称为AIM 2的分子（在黑素瘤2中不存在）对于介导由细胞质DNA引发的炎症反应至关重要。此外，被称为STING（干扰素基因刺激因子）的内质网相关蛋白被证明是促进响应于细胞内DNA和多种DNA病原体的IFN产生的关键。在这里，我们回顾了与外源DNA检测相关的最新发现，包括STING和AIM 2的重要性以及先天信号通路的激活。
The early detection of microbes is the responsibility of the innate immune system which has evolved to sense pathogen derived molecules such as lipopolysaccharides and non-self nucleic acid, to trigger host defense countermeasures. These sensors include the RIG-I-like helicase family (RLH) that specifically recognizes viral RNA, as well as the cytoplasmic, nucleotide binding oligermerization domain (NOD)-like receptor and Toll-like receptor (TLR) pathways that sense a variety of microbial derived molecules. Comprehending how the cell senses foreign DNA, generated by certain viruses, bacteria and possibly parasites has proven elusive but is of significant importance since such information could shed insight into the causes of microbial related disease, including viral associated cancers and autoimmune disorders. Plasmacytoid dendritic cells are known to utilize TLR9 to detect pathogen-associated DNA and to trigger the production of type I interferon (IFN), as well as other cytokines, although alternate key DNA detecting sensors remain to be identified. Recently however, a molecule referred to as AIM2 (absent in melanoma 2) was found to be essential for mediating inflammatory reactions triggered by cytoplasmic DNA. In addition, an endoplasmic reticulum associated protein referred to as STING (for Stimulator of Interferon Genes) was demonstrated as being pivotal for facilitating IFN production in response to intracelleular DNA and a variety of DNA pathogens. Here, we review recent discoveries relating to the detection of foreign DNA, including the importance of the STING and AIM2 and the activation of innate signaling pathways.
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影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
DOI：
10.1073/pnas.0909545106
发表时间：
2009-10-20
影响因子：
11.1
作者：
Choi, Myoung Kwon;Wang, ZhiChao;Taniguchi, Tadatsugu
通讯作者：
Taniguchi, Tadatsugu
影响因子：
64.5
作者：
Chien, Yuchen;Kim, Sungchan;White, Michael A.
通讯作者：
White, Michael A.
影响因子：
64.5
作者：
通讯作者：
--
DOI：
10.1126/science.1183021
发表时间：
2010-01-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Iwasaki A;Medzhitov R
通讯作者：
Medzhitov R