Insights into the Complement System of Tunicates: C3a/C5aR of the Colonial Ascidian Botryllus schlosseri.

Anna Peronato,Nicola Franchi,Loriano Ballarin

doi:10.3390/biology9090263

Abstract

As an evolutionary ancient component of the metazoan immune defense toolkit, the complement system can modulate cells and humoral responses of both innate and (in jawed vertebrates) adaptive immunity. All the three known complement-activation pathways converge on the cleavage of C3 to C3a and C3b. The anaphylatoxin C3a behaves as a chemokine in inflammatory responses, whereas C3b exerts an opsonic role and, ultimately, can activate the lytic pathway. C3aR, one of the mammalian receptors for C3a, is a member of the G-protein-coupled receptor family sharing seven transmembrane alpha helixes. C3aR can act as a chemokine and recruit neutrophils, triggering degranulation and respiratory burst, which initiates an inflammatory reaction. Mining the transcriptome of the colonial ascidian Botryllus schlosseri, we identified a transcript showing homology with both mammalian C3aR and C5aR. The gene (bsc3/c5ar) is actively transcribed in morula cells, the circulating immunocyte triggering the inflammatory reactions in response to the recognition of nonself. Its transcription is modulated during the recurrent cycles of asexual reproduction known as blastogenetic cycles. Moreover, the treatment of hemocytes with C3aR agonist, induces a significant increase in the transcription of BsC3, revealing the presence of an autocrine feedback system able to modulate the expression of C3 in order to obtain a rapid clearance of potentially dangerous nonself cells or particles. The obtained results support the previously proposed role of complement as one of the main humoral components of the immune response in tunicates and stress the importance of morula cells in botryllid ascidian innate immunity.

Highlights

Inflammation is one of the first lines of defense in the innate immune system of metazoans.It involves the recruitment of immunocytes to the infection sites, their extravasation, and consequent degranulation with the induction of cytotoxicity [1]
Since we already reported a significant increase of the amount of bsc3 transcription at TO with respect to early cycle (EC) [37], the obtained data are indicative of the presence of an additional control against the deleterious effects of prolonged complement activation
Our results demonstrate that a functional C3a/C5aR gene is present in the colonial ascidian B. schlosseri

Summary

Introduction

Inflammation is one of the first lines of defense in the innate immune system of metazoans. It involves the recruitment of immunocytes to the infection sites, their extravasation, and consequent degranulation with the induction of cytotoxicity [1]. The inflammatory events operate in tight association with the complement system (CS), one of the most ancient immune modulators of metazoans [2]. The CS leads to the cleavage of the core protein C3 into component proteins C3a and C3b [2,3]. The anaphylatoxin C3a, which shares many functional behaviors with the closely related molecules C4a and C5a, plays a central role in inflammatory response. C3a recruits and activates immunocytes, triggers degranulation, induces phagocytosis, and associated respiratory burst and reactive oxygen species (ROS) production. C3a works primarily by interacting with its receptor, known as C3a receptor (C3aR) [4,5,6]

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Discussion

Conclusion