Global Health Institute, École Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
Howard Hughes Medical Institute, Department of Molecular Biology, Center for Inflammation Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Science. 2019 Mar 8;363(6431). doi: 10.1126/science.aat8657.
DNA is highly immunogenic. It represents a key pathogen-associated molecular pattern (PAMP) during infection. Host DNA can, however, also act as a danger-associated molecular pattern (DAMP) and elicit strong inflammatory responses. The cGAS-STING pathway has emerged as a major pathway that detects intracellular DNA. Here, we highlight recent advances on how cGAS and STING mediate inflammatory responses and how these are regulated, allowing cells to readily respond to infections and noxious agents while avoiding the inappropriate sensing of self-DNA. A particular focus is placed on the role of cGAS in the context of sterile inflammatory conditions. Manipulating cGAS or STING may open the door for new therapeutic strategies for the treatment of acute and chronic inflammation relevant to many human diseases.
DNA 具有很强的免疫原性。它在感染过程中代表一种关键的病原体相关分子模式 (PAMP)。然而，宿主 DNA 也可以作为危险相关分子模式 (DAMP)，并引发强烈的炎症反应。cGAS-STING 途径已成为检测细胞内 DNA 的主要途径。在这里，我们重点介绍 cGAS 和 STING 如何介导炎症反应以及这些反应如何受到调节，使细胞能够迅速对感染和有害剂作出反应，同时避免对自身 DNA 的不当感知。特别关注 cGAS 在无菌炎症情况下的作用。操纵 cGAS 或 STING 可能为治疗与许多人类疾病相关的急性和慢性炎症的新治疗策略开辟了道路。
