Functional characterization of Siglec14 in facilitating innate defenses in Carassius cuvieri × Carassius auratus red var

Sialic acid-binding Ig-like lectin 14 (Siglec14) is a member of the Siglecs family, a group of immune system receptors characterized by their ability to recognize sialic acids, which are a type of carbohydrate commonly found on the surfaces of cells in mammals. However, the role of Siglec14 in the innate immunity of teleosts has not been extensively explored. For this purpose, our study focused on the identification and characterization of a classical Siglec14, designated as WR-Siglec14, derived from the hybrid fish Carassius cuvieri × Carassius auratus red var. Sequence analysis reveals WR-Siglec14 has the considerable homology with Siglec14 orthologs across various species, featuring the conserved immunoglobulin domains. We further investigated the expression patterns of WR-Siglec14 in response to pathogen exposure and observed significant upregulation in key immune-related tissues upon infection with Aeromonas hydrophila. Additionally, the study demonstrated that WR-Siglec14 enhanced the bactericidal activity and interacted with WR-DAP12. Moreover, we found treatment with WR-Siglec14 maintained higher numbers of goblet cells and mitigated apoptosis in the gut tissue during A. hydrophila infection. WR-Siglec14 also stimulated antimicrobial gene expression and reduced bacterial burdens in the fish, significantly improving survival rates against A. hydrophila infection. These results indicate that WR-Siglec14 plays the critical role in immune defense and gut barrier function against pathogen invasion in fish.