Complement system receptors C3aR and CR1 in Tunicates: ancient roots of immunocyte dialogue

Complement system is one of the most important humoral defense mechanism of innate immunity. Its evolutionary history is rooted in cnidarians where C3 molecules have been described. C3 is considered, in all taxa, the main protein of the complement system and the peptides C3a and C3b, derived from its proteolysis, are the effectors of all the complement-related responses towards microorganisms. These peptides have been described in many taxa, but only in Vertebrates the complement system behaviour was deeply investigated, where more than 30 proteins were described. Conversely, in invertebrates, no more than 10 proteins in few organisms have been identified, all belonging to only two pathways of complement activation: the alternative and the lectin pathway. Recently we focussed our attention on the complement system of the colonial ascidian Botryllus schlosseri. We identified C3 and the serine proteases associated with the alternative and lectin pathways. In the present work, we identified the main receptors of the activated C3: BsCR1 and BsC3aR. The former is the receptor of C3b; the latter of the anaphylotoxin C3a. The sequence and the structure of BsC3aR and BsCR1 are highly conserved. Both genes are constitutively transcribed; CR1 and C3aR are transcribed only in haemocytes, the former in circulating phagocytes and the latter in cytotoxic morula cells. . The different expression sites of CR1 and C3aR indicates a similarity with what reported in vertebrates, where C3 can contribute to the activation of phagocytes, and what happen in ascidians, where C3 is produced by morula cells which, through the complement system, can orchestrate a complex dialogue with phagocytes during the immune response.