Origin of the metazoan immune system: identification of the molecules and their functions in sponges.

During the evolutionary transition to Metazoa, cell-cell- as well as cell-matrix recognition molecules have been formed, which made a further step in evolution possible, the establishment of an immune system. Sponges [Porifera] represent the oldest still extant metazoan phylum and consequently testify to major features of the common metazoan ancestor, the Urmetazoa. Most studies with respect to evolution and phylogeny in sponges have been performed with the marine demosponges Suberites domuncula and Geodia cydonium. These animals possess effective defense systems against microbes and parasites which involve engulfment of bacteria into specific cells, but also signal transduction pathways which actively kill bacteria. Among those is the LPS-mediated pathway, with the stress-responsive kinases. In addition, sponges are provided with an interferon-related system, with the (2-5)A synthetase as controlling enzyme. Transplantation studies have been performed on tissue, as well as at the cellular level ("mixed sponge cell reaction assay") which demonstrate the complex molecular strategy by which sponges respond to allogeneic- and/or autogeneic signals. Among the molecules involved in histo(in)compatibility response of sponges, cytokines e.g., the allograft inflammatory factor 1, have been identified which control rejection of allografts. Furthermore, transcription factors, with Tcf-like factor as an example, have been identified which very likely control gene expression during histocompatibility reactions. The immune reactions in sponges can be modulated by FK506, a drug which has been successfully used as immunosuppressant in humans. One further surprising finding is the fact that G. cydonium has several molecules containing polymorphic Ig-like domains of the variable type. It is concluded that the successful evolutionary transition to the Metazoa, with the sponges as the oldest still extant phylum, and the subsequent rapid radiation into the other metazoan phyla, became possible because of the acquisition of modular molecules, involved in cell adhesion and the immune system.