How do the immune systems of aquatic creatures like fish adapt to their unique environments? A recent study from Huazhong Agricultural University offers an intriguing look into this question. It focuses on a type of immune system sensor known as Toll-like receptor 7 (TLR7), uncovering a remarkable evolutionary adaptation in fish. Unlike their land-based counterparts, these aquatic animals have a version of TLR7 that can detect not just one, but two types of genetic material from viruses. This serves as an alert system against viral threats, shedding light on the complexity of life in water and opening doors to understanding how immune responses have evolved across different species.

In this groundbreaking research led by Professor Jianguo Su, a team including Dr. Rui Jiang, Dr. Wentao Zhu, Dr. Zhiwei Liao, and Dr. Chunrong Yang, all from Huazhong Agricultural University, has discovered an evolutionary twist in the immune systems of fish and similar creatures. Published in the journal iScience, their research reveals that fish possess a unique version of TLR7. This receptor can detect both single-stranded and double-stranded genetic material from viruses, playing a crucial role in triggering defenses against viral and bacterial infections.

Professor Jianguo Su, the principal investigator, emphasized the importance of TLR7 in their study: “TLR7 is essential for detecting viral single-stranded genetic material and starting immune responses. Surprisingly, we found that in fish, TLR7 also reacts to double-stranded genetic material. Yet, how TLR7 manages to recognize this double-stranded material remains a mystery.” This insight underlines the novelty of their research in exploring previously unknown aspects of immune response mechanisms in aquatic life forms.

The study utilized innovative methods to investigate these mechanisms. They began by examining the Ctenopharyngodon idella TLR7 (CiTLR7), a receptor found in a type of fish called teleost. By conducting experiments, the team showed that both single-stranded and double-stranded genetic materials could bind to CiTLR7, triggering an immune response. This finding was significant as it showed that CiTLR7 could recognize and respond to a wider variety of viral signals than that was previously known.

Professor Su further clarified their findings: “Our research shows that CiTLR7 can detect both single-stranded and double-stranded genetic material, triggering an immune response. This indicates that CiTLR7 has an anti-viral function.” This simple yet effective experiment provided conclusive evidence of the receptor’s dual role.

The research team delved into identifying the specific areas in CiTLR7 that bind to double-stranded genetic material. Through advanced modeling and subsequent mutation analysis, they identified two critical sites, L29 and L811, as essential for recognizing double-stranded genetic material. Professor Su explained the importance: “CiTLR7-L29 and CiTLR7-L811 are crucial for binding to double-stranded genetic material. CiTLR7 detects viral genetic material, triggers anti-viral defenses, and thereby protects cells from viral infections.” This discovery was vital in understanding the precise interactions of CiTLR7 with different types of genetic material, a key step in unraveling the immune response in fish.

In exploring the evolutionary aspect, the team compared TLR7 from various vertebrates, including fish and higher tetrapods, to understand the evolutionary development of this receptor. Their findings showed that the ability to bind double-stranded genetic material was unique to pisciformes and not present in tetrapod vertebrates. This discovery suggests an evolutionary adaptation where the ability of TLR7 to sense double-stranded genetic material developed in lower vertebrates and was lost in higher ones.

This study not only enhances our understanding of the immune system in non-tetrapod vertebrates but also opens new avenues for exploring the evolutionary complexities of immune response mechanisms across different species. Future research is needed to explore further into the protein modification and regulatory mechanisms of TLR7, which could have significant implications in the fields of immunology and evolutionary biology.

In summary, the research conducted by Professor Jianguo Su and his team at Huazhong Agricultural University has illuminated a crucial aspect of the immune system in non-tetrapod vertebrates. It reveals the unique ability of pisciforme TLR7 to detect both single-stranded and double-stranded genetic material from viruses. This discovery has profound implications for our understanding of the evolution and function of the immune system in aquatic vertebrates.

JOURNAL REFERENCE

Rui Jiang, et al. “TLR7 neo-functionalizes to sense dsRNA and trigger antiviral and antibacterial immunity in non-tetrapod vertebrates.” iScience, 2023. DOI: https://doi.org/10.1016/j.isci.2023.108315

ABOUT THE AUTHOR

Jianguo Su, Professor in College of Fisheries, Huazhong Agricultural University, China. His research topic is Fish immunology. He engages in antiviral and antibacterial mechanisms, oral vaccines and biologics in fishes. He focuses on Toll-like receptor family, RIG-I-like receptor family, cytokines and novel antimicrobial peptides in grass carp. He is the Members of Executive Committee of the Asia Society of Developmental and Comparative Immunology, Professional Committee of Aquatic Animal Immunology, Chinese Fisheries Society, Professional Committee of Fish Diseases, Chinese Fisheries Society. He is the Editorial Boards for Developmental & Comparative Immunology, Comparative Immunology Reports. His publications include Cellular & Molecular Immunology, Science China Life Sciences, EMBO Reports, The Journal of Immunology, Journal of Virology, Journal of Biological Chemistry, Reviews in Aquaculture, iScience, etc.