Integrating AI in characterization receptor and construction signaling network for beta-glucan-engaged trained immunity in zebrafish [ChIP-seq]

While beta-glucan, a fungal cell wall component, is a known inducer of this process in zebrafish, the specific receptor responsible remains unidentified. Here, we identify C-type lectin domain-containing 1 (CLDC1), designated DrDectin-1, as the pivotal beta-glucan receptor in zebrafish through AI-driven bioinformatic screening based on mammalian Dectin-1.

Structural analysis suggests key beta-glucan binding residues (D182, Y183, H184). Using cldc1 knockout zebrafish in beta-glucan training and secondary infection models, combined with RNA-seq, H3K4me3 ChIP-seq, and virtual cell modeling, we demonstrate that CLDC1 mediates trained immunity via the Syk-Raf signaling pathways. Our findings identify the long-sought beta-glucan receptor in zebrafish and provide a comprehensive mechanistic framework for innate immune memory in teleosts, with implications for evolutionary immunology and disease management.