ArticleProceedings of the National Academy of Sciences of the United States of America2013
Toll-like receptor 9 and 21 have different ligand recognition profiles and cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 122 citations in OpenAlex.
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- Toll-like Receptor 3 is Required for Sensing Extracellular Double Stranded RNA in Salmonid Cells.Marine biotechnology (New York, N.Y.) · 2026Article
- Absence of Toll-like Receptor 21 (Biology · 2026Article
- Toll-like receptors in fish: evolution, structure, immune signaling, and translational prospects for adjuvant-based vaccine design in aquaculture.Frontiers in immunology · 2026Review
- CRATER tumor niches facilitate CD8Cell · 2025Article
- Reprogramming macrophages with R848-loaded artificial protocells to modulate skin and skeletal wound healing.Journal of cell science · 2024Article
- Effectiveness of dietary heat-killed Bacillus subtilis harboring plasmid containing 60 copies of CpG-ODN 1668 against Vibrio harveyi in Penaeus vannamei.Veterinary research communications · 2024Article
- TLR7 neo-functionalizes to sense dsRNA and trigger antiviral and antibacterial immunity in non-tetrapod vertebrates.iScience · 2023Article
- The Spike protein of SARS-CoV-2 signals via Tlr2 in zebrafish.Developmental and comparative immunology · 2023Article
- Transcriptome-wide analyses of early immune responses in lumpfish leukocytes upon stimulation with poly(I:C).Frontiers in immunology · 2023Article
- Immune response of DNA vaccinated-gilthead seabream (Frontiers in immunology · 2023Article
- Gene loss and co-option of toll-like receptors facilitate paternal immunological adaptation in the brood pouch of pregnant male seahorses.Frontiers in immunology · 2023Article
- Genome-Wide Identification, Characterization and Expression Analysis of Toll-like Receptors in Marbled Rockfish (International journal of molecular sciences · 2022Article
- Cyprinid-specific duplicated membrane TLR5 senses dsRNA as functional homodimeric receptors.EMBO reports · 2022Article
- Sharpening up tumor microenvironment to enhance the efficacy of immune checkpoint blockade on head and neck cancer using a CpG-oligodeoxynucleotide.Cancer immunology, immunotherapy : CII · 2022Article
- Adaptation and Cryptic Pseudogenization in Penguin Toll-Like Receptors.Molecular biology and evolution · 2022Article
- Multiomics analysis of soybean meal induced marine fish enteritis in juvenile pearl gentian grouper, Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂.Scientific reports · 2021Article
- TLR7 ligation augments hematopoiesis in Rps14 (uS11) deficiency via paradoxical suppression of inflammatory signaling.Blood advances · 2021Article
- CpG-ODN induced antimicrobial immunity in neonatal chicks involves a substantial shift in serum metabolic profiles.Scientific reports · 2021Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CpG-oligodeoxynucleotides (CpG-ODNs) are potent immune stimuli currently under investigation as antimicrobial agents for different species. Toll-like receptor (TLR) 9 and TLR21 are the cellular receptors of CpG-ODN in mammals and chickens, respectively. The avian genomes lack TLR9, whereas mammalian genomes lack TLR21. Although fish contain both of these genes, the biological functions of fish TLR9 and TLR21 have not been investigated previously. In this study, we comparatively investigated zebrafish TLR9 (zebTLR9) and TLR21 (zebTLR21). The two TLRs have similar expression profiles in zebrafish. They are expressed during early development stages and are preferentially expressed in innate immune function-related organs in adult fish. Results from cell-based activation assays indicate that these two zebrafish TLRs are functional, responding to CpG-ODN but not to other TLR ligands. zebTLR9 broadly recognized CpG-ODN with different CpG motifs, but CpG-ODN with GACGTT or AACGTT had better activity to this TLR. In contrast, zebTLR21 responded preferentially to CpG-ODN with GTCGTT motifs. The distinctive ligand recognition profiles of these two TLRs were determined by their ectodomains. Activation of these two TLRs by CpG-ODN occurred inside the cells and was modulated by UNC93B1. The biological functions of these two TLRs were further investigated. The CpG-ODNs that activate both zebTLR9 and zebTLR21 were more potent than others that activate only zebTLR9 in the activation of cytokine productions and were more bactericidal in zebrafish. These results suggest that zebTLR9 and zebTLR21 cooperatively mediate the antimicrobial activities of CpG-ODN. Overall, this study provides a molecular basis for the activities of CpG-ODN in fish.
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