Origin of the metazoan immune system: Identification of the molecules and their functions in sponges1

SYNOPSIS.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.

INTRODUCTION

Research activity focused on the elucidation of the cellular and molecular basis of immunity in sponges (phylum Porifera) was hampered by the fact that the phylogenetic position of these animals was uncertain. In 1899 (DeLage and Herouard, 1899) the Porifera had been grouped with the Metazoa, restricting them to a taxonomic position, the Spongiaires, separate from the rest of the multicellular animals. Prior to this attempt the sponges had been regarded as Corallines (Ellis, 1756; 92), Plant-Animals (Esper, 1794; vol. 2, p. 165) or as Animal-Plants (Pallas, 1787; vol. 2, p. 212). Intermittently, the Porifera were classified to the Protista/Protozoa (Haeckel, 1866; and Spencer, 1864; vol. 1, p. 302). Unfortunately the view that sponges are almost animals, Parazoa, is still even today often seen in textbooks (e.g., Pechenik, 2000), since sponges lack a nervous system, a "true" musculature and the basal lamina. It even remained unclear if Porifera share one common ancestor with other metazoan phyla (Christen et al., 1991). After analyzing protein sequences from sponges, especially those which comprise receptors, it was established that all Metazoa, including Porifera, are of monophyletic origin (Muller et al., 1994; Muller, 1995). In addition, it became obvious in the last five years that sponges do contain nervous elements, e.g., neuronal receptor (Perovic et al., 1999), and contractile systems, e.g., dynamic elements (Lorenz et al., 1996), as well as the basic structures of the basal lamina, e.g., integrin and collagen (Pancer et al., 1997; Schroder et al., 2000). Thus, the question arises as to whether the existing differences in the nervous system (lack of neurons), the musculature (lack of connecting muscular fibrils) and the basal lamina (lack of cell junctions) justify division of the Porifera into a separate subkingdom. Considering especially the complex immune system of sponges, which is closely related to that of higher Metazoa, especially the Deuterostomia, (see this review) a neutral term for the hypothetical ancestor of all metazoan phyla, the Urmetazoa, was proposed (Muller, 2001). This grouping is supported by the fact that the extracellular matrix molecules, as well as their corresponding cell surface receptors (Muller, 1997), had been the prerequisites for the evolution of an efficient immune system in Metazoa (Muller et al., 1999a).

It was the contribution of Metchnikoff (1892) who described the phagocytotic activity of sponge cells, archaeocytes, as a mechanism to eliminate non-self particles and, even more advanced, to encapsulate the foreign material within cell aggregates of the sponge prior to the elimination by "ablation" (p. 56-57). These abilities of sponges had been discussed by Metchnikoff in the context of inflammation processes, that proceed in Metazoa during infection. The major step in the elucidation of the cellular mechanisms by which the sponges eliminate non-self and accept self came from elegant experimental transplantation studies. In their extensive review Smith and Hildemann (1986) have grouped sponge alloimmune responses into two major rejection processes. Some species may form barriers to separate from non-self tissue; e.g., the marine sponge Axinella verrucosa (Buscema and van de Vyver, 1983) or the freshwater sponge Ephydatia muelleri (Mukai, 1992), while others may react by cytotoxic factors which destroy the transplant; e.g., the marine sponges Callyspongia diffusa (Hildemann et al., 1979) or Geodia cydonium (Pfeifer et al., 1992). Finally, the breakthrough in the discovery that immune mechanisms in sponges are highly similar to those, found in other metazoan phyla, came again after the application of molecular biological techniques (see Muller et al., 1999a).