Functional characterization of specialized immune cells in a cnidarian reveals an ancestral antiviral program.

Examining early-branching animal phyla can help reconstruct the evolutionary origins of immune cells. Here, we characterize immune-related cell programs in embryos of the sea anemone Nematostella vectensis, a model of Cnidaria, which diverged ~600 million years ago from other animals. Using a transgenic Nematostella reporter line expressing mCherry under the RLRb antiviral promoter, we identify a morphologically and transcriptomically distinct cell population activated by the viral mimic poly(I:C). These cells upregulate immune effector and regulator genes and show increased phagocytic activity. Bulk RNA sequencing of RLRb expressing cells and single-cell transcriptomics reveal gene regulatory programs expressed in specialized immune cells under basal conditions and upon activation. Comparing Nematostella's immune expression profile with that of stony corals treated with the immunostimulant 2'3'-Cyclic GMP-AMP demonstrate a conserved immune response across Hexacorallia. This study uncovers a cnidarian immune cell type involved in antiviral immunity, providing insights into the evolutionary history of innate immunity.