ArticleJournal of immunology (Baltimore, Md. : 1950)2009
The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 158 citations in OpenAlex.
- Toll-like receptors in fish: evolution, structure, immune signaling, and translational prospects for adjuvant-based vaccine design in aquaculture.Frontiers in immunology · 2026Review
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- Friend for the host foe for the guest: Evidence from probioticiMetaOmics · 2025Article
- Adopting orphan receptors: zebrafish Tlr4 homologs mediate responses to group IX/X transition metals.Frontiers in immunology · 2025Article
- Zebrafish do not have a calprotectin ortholog.PloS one · 2025Article
- TLR7 in channel catfish (Ictalurus punctatus) is expressed in the endolysosome and is stimulated by synthetic ssRNA analogs, imiquimod, and resiquimod.Developmental and comparative immunology · 2024Article
- Article
- Article
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- Pneumolysin promotes host cell necroptosis and bacterial competence during pneumococcal meningitis as shown by whole-animal dual RNA-seq.Cell reports · 2022Article
- Cloning of Toll-like Receptor 3 Gene fromGenes · 2022Article
- Lipopolysaccharide detection by the innate immune system may be an uncommon defence strategy used in nature.Open biology · 2022Review
- Genome-Wide Identification, Characterization and Expression Analysis of Toll-like Receptors in Marbled Rockfish (International journal of molecular sciences · 2022Article
- Review
- Tollip-deficient zebrafish display no abnormalities in development, organ morphology or gene expression in response to lipopolysaccharide.FEBS open bio · 2022Article
- A novel uveitis model induced by lipopolysaccharide in zebrafish.Frontiers in immunology · 2022Article
- An EngineeredInternational journal of molecular sciences · 2021Article
- Identification and Characterization of Zebrafish Tlr4 Coreceptor Md-2.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Zebrafish larvae as experimental model to expedite the search for new biomarkers and treatments for neonatal sepsis.Journal of clinical and translational science · 2021Review
- Modeling Virus-Induced Inflammation in Zebrafish: A Balance Between Infection Control and Excessive Inflammation.Frontiers in immunology · 2021Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
Abstract
Mammalian immune responses to LPS exposure are typified by the robust induction of NF-kappaB and IFN-beta responses largely mediated by TLR4 signal transduction pathways. In contrast to mammals, Tlr4 signal transduction pathways in nontetrapods are not well understood. Comprehensive syntenic and phylogenetic analyses support our hypothesis that zebrafish tlr4a and tlr4b genes are paralogous rather than orthologous to human TLR4. Furthermore, we provide evidence to support our assertion that the in vivo responsiveness of zebrafish to LPS exposure is not mediated by Tlr4a and Tlr4b paralogs because they fail to respond to LPS stimulation in vitro. Zebrafish Tlr4a and Tlr4b paralogs were also unresponsive to heat-killed Escherichia coli and Legionella pneumophila. Using chimeric molecules in which portions of the zebrafish Tlr4 proteins were fused to portions of the mouse TLR4 protein, we show that the lack of responsiveness to LPS was most likely due to the inability of the extracellular portions of zebrafish Tlr4a and Tlr4b to recognize the molecule, rather than to changes in their capacities to transduce signals through their Toll/IL-1 receptor (TIR) domains. Taken together, these findings strongly support the notion that zebrafish tlr4a and tlr4b paralogs have evolved to provide alternative ligand specificities to the Tlr immune defense system in this species. These data demonstrate that intensive examination of gene histories when describing the Tlr proteins of basally diverging vertebrates is required to obtain fuller appreciation of the evolution of their function. These studies provide the first evidence for the functional evolution of a novel Tlr.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.