Tick galactosyltransferases are involved in a-Gal synthesis and play a role during Anaplasma phagocytophilum infection and Ixodes scapularis tick vector development

The carbohydrate Gala1-3Galß1-(3)4GlcNAc-R (a-Gal) is produced in all mammals except for humans, apes and old world monkeys that lost the ability to synthetize this carbohydrate. Therefore, humans can produce high antibody titers against a-Gal. Anti-a-Gal IgE antibodies have been associated with tick-induced allergy (i.e. a-Gal syndrome) and anti-a-Gal IgG/IgM antibodies may be involved in protection against malaria, leishmaniasis and Chagas disease. The a-Gal on tick salivary proteins plays an important role in the etiology of the a-Gal syndrome. However, whether ticks are able to produce endogenous a-Gal remains currently unknown. In this study, the Ixodes scapularis genome was searched for galactosyltransferases and three genes were identified as potentially involved in the synthesis of a-Gal. Heterologous gene expression in a-Gal-negative cells and gene knockdown in ticks confirmed that these genes were involved in a-Gal synthesis and are essential for tick feeding. Furthermore, these genes were shown to play an important role in tick-pathogen interactions. Results suggested that tick cells increased a-Gal levels in response to Anaplasma phagocytophilum infection to control bacterial infection. These results provided the molecular basis of endogenous a-Gal production in ticks and suggested that tick galactosyltransferases are involved in vector development, tick-pathogen interactions and possibly the etiology of a-Gal syndrome in humans