Allergic reactions to tick saliva components in zebrafish model

Background Alpha-Gal syndrome (AGS) is a tick-borne food allergy caused by IgE antibodies against the glycan galactose-alpha-1,3-galactose (a-Gal) present in glycoproteins and glycolipids from mammalian meat. To advance in the diagnosis and treatment of AGS, further research is needed to unravel the molecular and immune mechanisms underlying this syndrome. The objective of this study is the characterization of tick salivary components and proteins with and without alpha-Gal modifications involved in modulating human immune response against this carbohydrate. Methods Protein and alpha-Gal content were determined in tick saliva components, and proteins were identified by proteomics analysis of tick saliva fractions. Pathophysiological changes were recorded in the zebrafish (Danio rerio) model after exposure to distinct Ixodes ricinus tick salivary components. Serum samples were collected from zebrafish at day 8 of exposure to determine anti-alpha-Gal, anti-glycan, and anti-tick saliva protein IgM antibody titers by enzyme-linked immunosorbent assay (ELISA). Results Zebrafish treated with tick saliva and saliva protein fractions combined with non-protein fractions demonstrated significantly higher incidence of hemorrhagic type allergic reactions, abnormal behavioral patterns, or mortality when compared to the phosphate-buffered saline (PBS)-treated control group. The main tick salivary proteins identified in these fractions with possible functional implication in AGS were the secreted protein B7P208-salivary antigen p23 and metalloproteases. Anti-alpha-Gal and anti-tick salivary gland IgM antibody titers were significantly higher in distinct saliva protein fractions and deglycosylated saliva group when compared with PBS-treated controls. Antiglycan antibodies showed group-related profiles. Conclusions Results support the hypothesis that tick salivary biomolecules with and without alpha-Gal modifications are involved in modulating immune response against this carbohydrate.

Automated summary

This study investigates the role of tick salivary components and proteins with and without alpha-Gal modifications in modulating the immune response against the carbohydrate. The results show that exposure to tick saliva leads to allergic reactions, abnormal behavior, and mortality in zebrafish. The antibody titers against alpha-Gal and tick salivary gland proteins are significantly higher in the saliva protein fractions and deglycosylated saliva group.