cJUN dependent innate immunity controls microbiome through selective phagocytosis in Nematostella

Innate immunity, traditionally viewed as non-specific, is increasingly recognized for its capacity to regulate microbial communities with precision. In the sea anemone Nematostella vectensis , we uncover a form of selective immunity mediated by nematosomes—motile immune cell clusters that preferentially phagocytose foreign Vibrio isolates while sparing native bacteria. We identify the transcription factor cJUN as essential for this process: CRISPR/Cas9-mediated knockout of cJUN impairs nematosome proliferation, reduces lysosomal activation, and alters microbiome composition by allowing colonization of non-native strains. These results link immune gene function to microbial selectivity and demonstrate that even early-diverging animals exhibit immune discrimination. Our findings challenge the classical dichotomy between innate and adaptive immunity and reveal that immune specificity may be evolutionarily ancient. This work establishes Nematostella as a model for studying microbiome-induced innate immune training and highlights conserved mechanisms that maintain host-microbe homeostasis.