All lifeforms have developed highly sophisticated systems equipped to detect altered self and non-self nucleic acids (NA). In vertebrates, NA-sensing receptors safeguard the integrity of the organism by detecting pathogens, dyshomeostasis and damage, and inducing appropriate responses to eliminate pathogens and reconstitute homeostasis. Effector mechanisms include i) immune signaling, ii) restriction of NA functions such as inhibition of mRNA translation, and iii) cell death pathways. An appropriate effector response is necessary for host defense, but dysregulated NA-sensing can lead to devastating autoimmune and autoinflammatory disease. Their inherent biochemical similarity renders the reliable distinction between self NA under homeostatic conditions and altered or exogenous NA particularly challenging. In this review, we provide an overview of recent progress in our understanding of the closely coordinated and regulated network of innate immune receptors, restriction factors, and nucleases to effectively respond to pathogens and maintain host integrity.

所有生命形式都开发了高度复杂的系统，能够检测改变的自身和非自身核酸 (NA)。在脊椎动物中，NA 感应受体通过检测病原体、体内平衡失调和损伤，并诱导适当的反应以消除病原体和重建体内平衡来保护生物体的完整性。效应机制包括 i) 免疫信号，ii) 限制 NA 功能，例如抑制 mRNA 翻译，和 iii) 细胞死亡途径。宿主防御需要适当的效应反应，但 NA 感应失调可导致破坏性自身免疫和自身炎症性疾病。它们固有的生化相似性使得稳态条件下自身 NA 与改变的或外源性 NA 之间的可靠区分变得特别具有挑战性。在这篇评论中，