Complement System Dynamics in Teleost Immunity

The complement system in teleost fish constitutes a cornerstone of innate defence, integrating classical, lectin and alternative activation routes to eliminate pathogens and shape inflammatory outcomes. Teleost genomes often harbour multiple paralogues of central components such as C3 and factor B/C2, reflecting gene duplication events that confer functional diversity. Activation of C3 yields the opsonin C3b and the anaphylatoxin C3a, which together promote phagocytosis, cell recruitment and direct lysis via membrane attack complexes. Regulatory proteins, including factor H and CD46, fine-tune this cascade to prevent host tissue damage. Emerging evidence highlights cross-talk between complement fragments and adaptive lymphocytes, notably in teleost B cells, underscoring a bridging of innate and adaptive responses. This dynamic network not only underlies resistance to bacterial and viral challenge in wild populations but also informs strategies to enhance vaccine efficacy and disease management in aquaculture species globally.

Research from Nature Portfolio

Recent studies have demonstrated that membrane cofactor protein CD46 in teleosts binds factor I to inactivate C3b and limit complement-mediated damage to host cells. Recombinant CD46 was shown to protect leukocytes from complement-induced lysis and, intriguingly, serve as a bacterial receptor, facilitating pathogen adhesion under controlled conditions. Modulation of CD46 levels influenced tissue dissemination of bacteria in vivo, revealing dual roles in complement regulation and infection dynamics. These findings establish CD46 as a pivotal regulator of complement homeostasis with potential as a target for controlling infectious disease in fish.

Research from all publishers

A transcriptomic analysis of grass carp complement factor B/C2 variants during viral infection revealed stage-specific up-regulation of BF/C2A and BF/C2B isoforms, implicating these molecules in the early antiviral response and in driving inflammation at later stages. In Japanese flounder, characterisation of C3 and its fragment C3a uncovered broad bacterial binding by C3 and direct bacteriolytic activity, while C3a was shown to recruit peripheral blood leukocytes and enhance resistance to bacterial challenge. Investigations in Nile tilapia further demonstrated that recombinant C3 alleviates tissue pathology after Streptococcus agalactiae infection and promotes monocyte/macrophage phagocytosis, underscoring C3’s central role in coordinating inflammation and cellular defences. Together, these studies illustrate the functional diversification of complement molecules in teleost immunity and their potential application in disease control.

Complement System Dynamics in Teleost Immunity publication trend

The graph below shows the total number of articles in complement system dynamics in teleost immunity across all publications each year (not limited to Nature Index journals).

Technical terms

Complement system: A proteolytic cascade of plasma proteins that enhances pathogen clearance through opsonisation, inflammation and lysis.

Teleost: A diverse group of ray-finned fishes representing the largest infraclass of vertebrates.

C3: The central complement component whose activation generates C3b for opsonisation and C3a for inflammatory signalling.

C3a: An anaphylatoxin fragment of C3 that acts as a chemoattractant and modulator of immune cells.

BF/C2: Factor B/C2 family proteins that participate in alternative and classical pathway C3 convertase formation.

CD46: A membrane cofactor that binds factor I to inactivate C3b and regulate complement activity on host cells.

Phagocytosis: The uptake and destruction of microorganisms by specialised immune cells.

References

1. Preliminary study of BF/C2 on immune mechanism of grass carp against GCRV infection. BMC Genomics (2024).
2. The Evolution and Appearance of C3 Duplications in Fish Originate an Exclusive Teleost c3 Gene Form with Anti-Inflammatory Activity. PLOS ONE (2014).
3. A teleost CD46 is involved in the regulation of complement activation and pathogen infection. Scientific Reports (2017).
4. Complement C3 and Activated Fragment C3a Are Involved in Complement Activation and Anti-Bacterial Immunity. Frontiers in Immunology (2022).
5. Complement C3 Regulates Inflammatory Response and Monocyte/Macrophage Phagocytosis of Streptococcus agalactiae in a Teleost Fish. International Journal of Molecular Sciences (2022).
6. Complement C3a Enhances the Phagocytic Activity of B Cells Through C3aR in a Fish. Frontiers in Immunology (2022).