Examining early-branching animal phyla can help reconstructing the evolutionary origin of animal immune cells. Here we characterized the immune related cell program in the sea anemone Nematostella vectensis, a model organism representing the phylum Cnidaria that diverged ~600 million years ago from the rest of animals. By using a Nematostella transgenic reporter line expressing mCherry under the RLRb antiviral promoter we show that cells fluorescent upon stimulation with the viral mimic poly(I:C) are morphologically and transcriptomically distinct. These cells exhibit upregulation of immune effector and regulator genes. Cellular assays revealed an increase in phagocytic activity upon poly(I:C) treatment in this cell population. Lastly, we used a combination of immunofluorescent staining followed by FACS and bulk RNA sequencing, accompanied by single-cell transcriptomic analysis, to reveal the gene regulatory programs associated with immune cells in Nematostella. Comparing the sea anemone immune expression profile with gene expression of stony corals treated with the immunostimulant 2′3′-Cyclic GMP-AMP revealed remarkable similarity, suggesting that the immune response to viral challenge is conserved across the cnidarian class Hexacorallia. Altogether, this research uncovers the characteristics of a novel cnidarian immune cell type involved in antiviral immunity and offers insights into the evolutionary history of the innate immune system.Competing Interest StatementThe authors have declared no competing interest.Footnotes* https://doi.org/10.6084/m9.figshare.28266230* https://doi.org/10.6084/m9.figshare.28265126...

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

10.1101/2025.01.24.634691