The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation

This primer focuses on a recently diagnosed tick-borne allergic disease known as the alpha-Gal syndrome (AGS). Tick bites induce in humans high levels of IgE antibodies against the carbohydrate Gal alpha 1-3Gal beta 1-(3)4GlcNAc-R (alpha-Gal) present on tick salivary glycoproteins and tissues of non-catarrhine mammals, leading to the AGS in some individuals. This immune response evolved as a conflict and cooperation between ticks and human hosts including their gut microbiota. The conflict is characterized by the AGS that mediate delayed anaphylaxis to red meat consumption and certain drugs such as cetuximab, and immediate anaphylaxis to tick bites. The cooperation is supported by the capacity of anti-alpha-Gal IgM and IgG antibody response to protect against pathogens with alpha-Gal on their surface. Despite the growing diagnosis of AGS in all world continents, many questions remain to be elucidated on the tick proteins and immune mechanisms triggering this syndrome, and the protective response against pathogen infection elicited by anti-alpha-Gal antibodies. The answer to these questions will provide information for the evaluation of risks, diagnosis and prevention of the AGS, and the possibility of using the carbohydrate alpha-Gal to develop vaccines for the control of major infectious diseases.