Traditionally, immunological memory—the body’s ability to remember an infection and respond more effectively in the future—was thought to be exclusive to vertebrates. However, recent research is dismantling this paradigm, revealing that organisms such as mollusks possess a sophisticated long-term defense system, despite lacking antibodies and T and B lymphocytes.
A recent comparative study published by researchers from Zhejiang Shuren University and Hangzhou Medical College has delved into the mechanisms of “trained immunity” in two of the most critical groups for aquaculture and marine ecosystems: bivalves (such as oysters, clams, and mussels) and gastropods (such as abalones and snails). These findings not only broaden our understanding of invertebrate immunology but also provide promising tools for health management in aquaculture.
Key conclusions
- Although they lack an adaptive immune system like vertebrates, bivalve and gastropod mollusks can “remember” pathogens through a mechanism called trained immunity.
- Bivalves (oysters, mussels) primarily base their immunological memory on the complement system and lectins, whereas gastropods (snails, abalones) utilize special proteins called FREPs.
- Bivalves have been shown to pass this protection to their offspring, a phenomenon known as transgenerational immune priming (TGIP), which opens new avenues for aquaculture.
- Understanding these mechanisms allows for the development of immunostimulants and management strategies to protect mollusk crops against devastating diseases, such as the ostreid herpesvirus (OsHV-1).
The pillars of mollusk immunity: Hemocytes and humoral defenses
The mollusk immune system is built on two pillars: cellular immunity, led by hemocytes, and humoral immunity, which includes a range of molecules dissolved in their hemolymph.
- Cellular Immunity: Hemocytes are the primary immune cells in mollusks. They are mainly divided into granulocytes, which have a strong phagocytic capacity (engulfing pathogens), and hyalinocytes, which are more involved in signaling and cytotoxic responses. Gastropods also feature specific cell types like spread hemocytes (SHs) and round hemocytes (RHs) with specialized functions.
- Humoral Immunity: Mollusks deploy an arsenal of molecules to recognize and neutralize invaders. They use pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and lectins, to identify common molecular structures in pathogens (PAMPs). Once a threat is detected, signaling cascades are activated, culminating in the production of effectors like antimicrobial peptides (AMPs) and lysozymes.
The major revelation is that after a first encounter with a pathogen, mollusks can mount a faster and more robust secondary response. This phenomenon, known as trained immunity or immune priming, is based on shared mechanisms but with notable differences between bivalves and gastropods.
Common mechanisms
- Gene Expression Reprogramming: Following an infection, certain immunity-related genes remain in an “alert” state. Upon a second exposure, these genes are activated more rapidly and potently. Studies on oysters (Crassostrea gigas) have shown that after a second challenge with the bacterium Vibrio splendidus, key pathway genes like those for TLRs and MAPK are overexpressed.
- Epigenetic Modifications: Epigenetics acts like a switch that turns genes on or off without altering the DNA sequence. In mollusks, modifications to histones (the proteins that package DNA), such as the trimethylation of lysine 4 on histone 3 (H3K4me3), leave a lasting “mark” on immune genes, facilitating their future activation. This has been observed in oysters, where H3K4me3 keeps genes like CgTLR3 active.
- Metabolic Reprogramming: To sustain a stronger immune response, cells require more energy. Mollusks reprogram their metabolism, for instance by increasing glycolysis, to provide the necessary fuel for phagocytosis and other hemocyte functions.
Key differences: The “weapons” of each group
Although the underlying mechanisms are similar, the effector molecules each group uses to execute this immunological memory are distinct:
- Bivalves: Their defense relies heavily on the complement system and a great diversity of C-type lectins (CTLs). These molecules act as opsonins (marking pathogens for elimination) and activate cascades that lead to the invader’s destruction.
- Gastropods: Their distinctive feature is the use of fibrinogen-related proteins (FREPs). These molecules are incredibly diverse and can recognize a wide range of pathogens. They are believed to play a central role in the specificity of the immune response in these animals.
Inheriting immunity: Transgenerational priming in bivalves
One of the most fascinating implications with the greatest potential for aquaculture is the discovery of Transgenerational Immune Priming (TGIP) in bivalves. It has been shown that mother oysters exposed to certain immune stimuli (like poly(I:C), a viral RNA analog) can transfer that protection to their offspring.
Larvae from “immunized” parents exhibit significantly higher survival rates against pathogens like the devastating Ostreid herpesvirus 1 (OsHV-1). This phenomenon, likely mediated by the transfer of immune factors or epigenetic marks through gametes, offers a cost-effective and non-invasive strategy to protect larval stages, which are the most vulnerable in cultivation cycles.
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Practical applications: From basic science to the aquaculture farm
Detailed knowledge of immunological memory in mollusks opens up a range of practical applications to strengthen aquaculture:
- Development of Immunostimulants: Diets or immersion treatments can be formulated with immunostimulants (such as inactivated PAMPs) to “train” the mollusk immune system and prepare it for future infections.
- Broodstock Management: Applying immune conditioning protocols to broodstock, leveraging TGIP, can generate cohorts of larvae with enhanced innate resistance.
- Targeted “Vaccines”: Although not vaccines in the traditional sense, exposure to inactivated viral antigens from OsHV-1 has been shown to induce a protective immune response in oyster hemocytes, laying the groundwork for developing priming “vaccines.”
Despite these advances, challenges remain, such as standardizing immunostimulation protocols and identifying specific molecular markers for trained immunity. However, the evidence is clear: mollusks possess a more complex and potent immunological memory than we once imagined—a tool that modern aquaculture can and must leverage to ensure more sustainable and resilient production.
Contact
Keda Chen
Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University
Hangzhou, China.
Email: chenkd@zjsru.edu.cn
Reference (open access)
Li, H., Li, H., Zhao, L., Xu, J., Li, X., Zhao, Q., Zhang, Y., Shao, Y., Wang, R., Wang, J., Lin, L., Yao, X., Zhang, X., & Chen, K. (2025). A comparative analysis of immune memory in bivalve and gastropod Mollusks: From mechanistic insights to practical applications. Aquaculture, 743092. https://doi.org/10.1016/j.aquaculture.2025.743092
Editor at the digital magazine AquaHoy. He holds a degree in Aquaculture Biology from the National University of Santa (UNS) and a Master’s degree in Science and Innovation Management from the Polytechnic University of Valencia, with postgraduate diplomas in Business Innovation and Innovation Management. He possesses extensive experience in the aquaculture and fisheries sector, having led the Fisheries Innovation Unit of the National Program for Innovation in Fisheries and Aquaculture (PNIPA). He has served as a senior consultant in technology watch, an innovation project formulator and advisor, and a lecturer at UNS. He is a member of the Peruvian College of Biologists and was recognized by the World Aquaculture Society (WAS) in 2016 for his contribution to aquaculture.
