An ancient role for conserved innate immunity transcription factors in holobiont self-recognition

Animal innate immunity may have evolved to regulate host-symbiont interactions using ancient and highly conserved animal transcription factors (TFs). We test this proposition by comparing cellular and transcriptional responses of a marine sponge presented with either native symbiotic or foreign bacteria. In contrast to foreign bacteria, experimentally introduced symbionts are quickly transported across the sponge epithelial boundary to underlying phagocytic amoebocytes. Numerous conserved immunity TFs, including NF-κB, IRF, STAT, AP-1, ETS, SMAD and nuclear receptors, pattern recognition receptors (PRRs) and signaling pathways are simultaneously activated. IRF translocates to the nuclei of amoebocytes that have engulfed the symbionts, followed shortly after by NF-κB, suggesting that both are critical to symbiont recognition. Nuclear localisation of STAT occurs in cells that do not have the symbionts. Foreign bacteria, in contrast, are internalised more slowly and do not induce the nuclear translocation of NF-κB, IRF or STAT, nor do they induce the upregulation of most other immunity genes. Instead, they induce a xenobiotic response. These findings suggest that the shared ancestor of sponges and other living animals used deeply conserved innate immunity TFs to recognise and maintain a beneficial microbiome.