DNA damage and innate immunity: links and trade-offs

• Immune DNA sensors signal the presence of damaged or foreign DNA.
• DNA damage sensors and the DDR are coupled to innate immune activation.
• DDR-driven immune responses contribute to age-related pathologies, including cancer.

To counteract DNA damage, cells employ genome maintenance pathways that are directed inward, relentlessly to scan and repair the genome. Adaptive and innate immune mechanisms are often directed outward, protecting self against pathogens. Recent work has revealed direct links between innate immune signaling and the DNA damage response (DDR). Here we review current understanding of the mechanism by which cells sense damaged and foreign DNA. We examine the functional role of DNA damage signaling in immune activation and discuss the relevance of these processes to DNA damage-driven chronic inflammation in disease and in aging.