Search

The knowledge of comparative and developmental immunobiology has grown over the years and has been strengthened by the contributions of multi-omics research. High-performance microscopy, flow cytometry, scRNA sequencing, and the increased capacity to handle complex data introduced by machine learning have allowed the uncovering of aspects of great complexity and diversity in invertebrate immunocytes, i.e., immune-related circulating cells, which until a few years ago could only be described in terms of morphology and basic cellular functions, such as phagocytosis or enzymatic activity. Today, invertebrate immunocytes are recognized as sophisticated biological entities, involved in host defense, stress response, wound healing, organ regeneration, but also in numerous functional aspects of organismal life not directly related to host defense, such as embryonic development, metamorphosis, and tissue homeostasis. The multiple functions of immunocytes do not always fit the description of invertebrate organisms as simplified biological systems compared to those represented by vertebrates. However, precisely the increasing complexity revealed by immunocytes makes invertebrate organisms increasingly suitable models for addressing biologically significant and specific questions, while continuing to present the undeniable advantages associated with their ethical and economic sustainability. [ABSTRACT FROM AUTHOR]

The complement system is a pivotal component of innate immunity, extensively studied in vertebrates but also present in invertebrates. This study explores the existence of a terminal complement pathway in the tunicate Botryllus schlosseri, aiming to understand the evolutionary integration of innate and adaptive immunity. Through transcriptome analysis, we identified a novel transcript, BsITCCP, encoding a protein with both MACPF and LDLa domains—a structure resembling that of vertebrate C9 but with a simpler organization. Phylogenetic reconstruction positions BsITCCP between invertebrate perforins and vertebrate terminal complement proteins, suggesting an evolutionary link. Localization studies confirmed that bsitccp is transcribed in cytotoxic morula cells (MCs), which are also responsible for producing other complement components like BsC3, BsMBL, BsMASP, and BsBf. Functional assays demonstrated that bsitccp transcription is upregulated in response to nonself challenges and is dependent on BsC3 activity; inhibition of BsC3 led to a significant reduction in BsITCCP expression. Electron microscopy revealed that MCs form contact with perforated yeast cells, indicating a possible mechanism of cell lysis similar to the immunological synapse observed in vertebrates. These findings suggest that a C3-governed lytic complement pathway exists in B. schlosseri, challenging the assumption that a C5 ortholog is necessary for such a pathway. This work enhances our understanding of the evolution of the complement system and suggests that invertebrates possess a terminal complement complex capable of mediating cell lysis, regulated by C3. Future studies will focus on confirming the pore-forming ability of BsITCCP and its role in the immunological synapse. [ABSTRACT FROM AUTHOR]