cGAS-STING dependent immunity in insects: insights from Drosophila flies

The cGAS-STING pathway constitutes an evolutionarily ancient antiviral defense mechanism, originating in bacteria. It is conserved in most animals, although with some differences. In insects, the model Drosophila melanogaster provides unique opportunities to decipher the function and regulation of this important pathway in hosts beyond mammals and shed light on its evolution. Here, we review recent advances in Drosophila that clarify the relationship between the cGAS-STING and IMD pathways, which both act through the NF-κB transcription factor Relish. We next consider the expansion of the cGLR family in Drosophila flies and the unexpected discovery of new cyclic dinucleotides (CDNs) besides cGAMP. We present the contribution of these CDNs in induction of systemic immunity and immune training in flies and discuss the conservation of these properties in other insects.