Program in Innate Immunity, Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
Eur J Immunol. 2014 Mar;44(3):634-40. doi: 10.1002/eji.201344127. Epub 2014 Jan 13.
The presence of DNA in the cytoplasm of mammalian cells is perceived as a danger signal, alerting the host to the presence of microbial infection. In response to the detection of cytoplasmic DNA, the immune system mounts a programed response that involves the transcription of anti-viral genes such as type I interferons and production of inflammatory cytokines such as IL-1β. The recent discovery of the cGAS-cGAMP second messenger pathway as well as IFI16 and additional sensors collectively provide critical insights into the molecular basis behind the sensing of cytoplasmic DNA. The insights obtained from these important discoveries could unveil new avenues to understand host-immunity, improve vaccine adjuvancy, and allow development of new treatments for inflammatory diseases associated with abberrant sensing of DNA.
哺乳动物细胞质中 DNA 的存在被视为危险信号,提醒宿主存在微生物感染。细胞质 DNA 检测后,免疫系统会启动程序性反应,转录抗病毒基因(如 I 型干扰素)并产生炎症细胞因子(如 IL-1β)。最近发现 cGAS-cGAMP 第二信使途径以及 IFI16 和其他传感器,共同为细胞质 DNA 检测的分子基础提供了重要见解。这些重要发现提供的见解可能为理解宿主免疫、改善疫苗佐剂以及开发与 DNA 异常感知相关的炎症性疾病的新疗法开辟新途径。