Adopting orphan receptors: zebrafish Tlr4 homologs mediate responses to group IX/X transition metals.

ABSTRACT: TLR4 is the prototype immune receptor and central to infection defense via detecting lipopolysaccharide (LPS). Surprisingly, the impacts of LPS upon the TLR4 homologs in zebrafish, an important animal model, are equivocal and the function of TLR4 homologs across all fishes remains debatable. Recent work suggests zebrafish Tlr4 mediates ototoxic responses to a platinum-based chemotherapeutic. This prompts our hypothesis that Tlr4 detects group IX/X transition metals and thus has conserved roles with human TLR4 mediating allergic responses to nickel. Here, we use the larval zebrafish lateral line model to demonstrate (sub-)micromolar Ni, Co and Pt are ototoxic in a dose-dependent manner. TLR4 homologs are required for this toxicity because Tlr4 knockdown via CRISPR significantly reduced the

SUBMITTER: Fox APD 

PROVIDER: S-EPMC12689318 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature