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Significance Cyclic dinucleotides are signaling molecules that originated in bacteria and were subsequently acquired and co-opted by animals for immune signaling. The major cyclic dinucleotide signaling pathway in mammals results in the production of antiviral molecules called interferons. Invertebrates such as sea anemones lack interferons, and thus it was unclear whether cyclic dinucleotide signaling would play a role in immunity in these animals. Here, we report that in the anemoneNematostella vectensis , cyclic dinucleotides activate both antiviral and antibacterial immune responses and do so through a conserved pathway. These results provide insights into the evolutionary origins of innate immunity and suggest a broader ancestral role for cyclic dinucleotide signaling that evolved toward more specialized antiviral functions in mammals.

The cyclic dinucleotide 2′3′-cGAMP induces a broad antibacterial and antiviral response in the sea anemone Nematostella vectensis