Evidence of a Lytic Pathway in an Invertebrate Complement System: Identification of a Terminal Complement Complex...

Area of Science:

• Immunology
• Evolutionary Biology
• Marine Biology

Background:

• The complement system is crucial for innate immunity, with its invertebrate forms poorly understood.
• Vertebrate terminal complement pathways involve C5 and C9 for cell lysis.
• Tunicates offer insights into immune system evolution between invertebrates and vertebrates.

Purpose of the Study:

• To investigate the presence and function of a terminal complement pathway in the tunicate Botryllus schlosseri.
• To understand the evolutionary integration of innate and adaptive immunity components.
• To identify novel complement proteins and their roles in invertebrate immunity.

Main Methods:

• Transcriptome analysis to identify novel complement genes.
• Phylogenetic reconstruction to determine evolutionary relationships.
• Immunolocalization studies using cytotoxic morula cells.
• Functional assays to assess gene expression and pathway dependence.
• Electron microscopy to visualize cellular interactions.

Main Results:

• A novel transcript, BsITCCP, encoding a MACPF/LDLa domain protein, was identified.
• BsITCCP is transcribed in cytotoxic morula cells and its expression is upregulated upon nonself challenge.
• BsITCCP expression is dependent on the complement component BsC3.
• Morula cells form contacts with target cells, suggesting a lytic mechanism.

Conclusions:

• Botryllus schlosseri possesses a C3-regulated terminal complement pathway for cell lysis.
• This pathway challenges the necessity of a C5 ortholog for complement-mediated lysis.
• The findings suggest a conserved evolutionary origin of terminal complement complexes in invertebrates.
• This study advances understanding of complement system evolution and invertebrate immune strategies.