Innate immune signaling in a sponge reveals ancient origin of host-symbiont recognition

Innate immunity in animals functions both to defend against pathogens and to regulate interactions with beneficial microbes. Although these dual roles suggest deep evolutionary roots, it remains unclear whether ancestral functions of the immune system were primarily for protection or for maintaining symbiotic partnerships. Here, we address this question using the marine sponge Amphimedon queenslandica , which belongs to an early-branching metazoan lineage, by comparing cellular and transcriptional responses to symbiotic and non-symbiotic bacteria. We show that symbionts are rapidly internalized across the epithelial boundary and elicit a swift and pronounced activation of innate immune transcription factors (TFs), including NF-κB, IRF, and STAT, as well as associated pattern recognition receptors (PRRs) and signaling pathways. Both IRF and NF-κB quickly translocate to the nuclei of amoebocytes that are engulfing symbionts, consistent with conserved roles in host–symbiont recognition. In contrast, non-symbiotic bacteria are internalized more slowly and fail to induce comparable immune activation or TF nuclear translocation. These results indicate that the last common ancestor of sponges and other animals already possessed a complex innate immune system capable of distinguishing among bacterial partners, suggesting that immune regulation of symbiosis is an ancient feature of animal evolution.