The pathological roles of bacterial DNA have been documented many decades ago. Bacterial DNAs are different from mammalian DNAs; the latter are heavily methylated. Mammalian cells have sensors such as TLR-9 to sense the DNAs with nonmethylated CpGs and distinguish them from host DNAs with methylated CpGs. Further investigation has identified many other types of DNA sensors distributed in a variety of cellular compartments. These sensors not only sense foreign DNAs, including bacterial and viral DNAs, but also sense damaged DNAs from the host cells. The major downstream signalling pathways includeTLR-9-MyD88-IKKa-IRF-7/NF-κB pathways to increase IFN/proinflammatory cytokine production, STING-TBK1-IRF3 pathway to increase IFN-beta, and AIM2-ASC-caspas-1 pathway to release IL-1beta. The major outcome is to activate host immune response by inducing cytokine production. In this review, we focus on the roles and potential mechanisms of DNA sensors and downstream pathways in sepsis. Although bacterial DNAs play important roles in sepsis development, bacterial DNAs alone are unable to cause severe disease nor lead to death. Priming animals with bacterial DNAs facilitate other pathological factors, such as LPS and other virulent factors, to induce severe disease and lethality. We also discuss compartmental distribution of DNA sensors and pathological significance as well as the transport of extracellular DNAs into cells. Understanding the roles of DNA sensors and signal pathways will pave the way for novel therapeutic strategies in many diseases, particularly in sepsis.

中文翻译：

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细菌 DNA 在脓毒症发展中的核心作用和可能机制。

细菌 DNA 的病理作用在几十年前就已有记载。细菌 DNA 不同于哺乳动物 DNA；后者被严重甲基化。哺乳动物细胞具有传感器，如 TLR-9，可感知带有非甲基化 CpG 的 DNA，并将它们与带有甲基化 CpG 的宿主 DNA 区分开来。进一步的研究已经确定了许多其他类型的 DNA 传感器分布在各种细胞隔室中。这些传感器不仅能感知外来 DNA，包括细菌和病毒 DNA，还能感知来自宿主细胞的受损 DNA。主要下游信号通路包括TLR-9-MyD88-IKKa-IRF-7/NF- κB 通路增加 IFN/促炎细胞因子的产生，STING-TBK1-IRF3 通路增加 IFN-β，AIM2-ASC-caspas-1 通路释放 IL-1β。主要结果是通过诱导细胞因子产生来激活宿主免疫反应。在这篇综述中，我们关注 DNA 传感器和下游通路在败血症中的作用和潜在机制。尽管细菌 DNA 在败血症的发展中起着重要作用，但单独的细菌 DNA 既不能导致严重的疾病，也不能导致死亡。用细菌 DNA 启动动物会促进其他病理因素，如 LPS 和其他毒力因素，从而诱发严重的疾病和致死率。我们还讨论了 DNA 传感器的区室分布和病理意义以及细胞外 DNA 向细胞的转运。