Cyclic dinucleotides at the forefront of innate immunity

Cyclic dinucleotides (CDNs) have emerged as ubiquitous signaling molecules in all domains of life. In eukaryotes, CDN signaling systems are evolutionarily ancient and have developed to sense and respond to pathogen infection. On the other hand, dysregulation of these pathways has been implicated in the pathogenesis of autoimmune diseases. Thus, CDNs have garnered major interest over recent years for their ability to elicit potent immune responses in the eukaryotic host. Similarly, ancestral CDN-based signaling systems also appear to confer immunological protection against infection in prokaryotes. Therefore, a better understanding of the host processes regulated by CDNs will be of tremendous value in many areas of research. Here, we aim to review the latest discoveries and recent trends in CDN research with a particular focus on the molecular mechanisms by which these small molecules mediate innate immunity.