The Zebrafish Model for Alpha-Gal Syndrome

Zebrafish (Danio rerio) has emerged as a robust vertebrate model for studying immune and allergic disorders, including food allergies. The alpha-Gal syndrome (AGS) is a tick-borne allergy characterized by an IgE-mediated delayed hypersensitivity to the oligosaccharide galactose-α-1,3-galactose (α-Gal), which is present in tick saliva and mammalian-derived foods and drugs. This chapter describes the experimental procedures used to establish and analyze the validated zebrafish model for AGS. Adult zebrafish were intramuscularly injected with Ixodes ricinus tick saliva and maintained on a mammalian meat-based diet to induce allergic responses. Clinical manifestations were monitored and correlated with serum anti-α-Gal IgM titers measured by ELISA, while the intestinal expression of allergic and immune biomarkers (ctss2.1, prkdc, il1b, il4, tnfα, tlr2, c3a, and ifn1) was analyzed by RT-qPCR. This animal model successfully reproduces key features of AGS such as delayed allergic reactions (hemorrhagic-type), altered behavior, and increased mortality, accompanied by elevated anti-α-Gal IgM antibody levels and modulation of immune gene expression. Importantly, zebrafish also enables the testing of specific salivary biomolecules from ticks or other arthropods to evaluate their allergenic potential. Overall, the zebrafish model provides a reproducible and cost-effective in vivo platform to elucidate molecular mechanisms underlying AGS and arthropod-induced allergies.