Why do tick bites induce an allergy to red meat in humans?

Until now, it was generally accepted that the ticks that cause alpha-gal syndrome acquire alpha-gal molecules from the blood of animals they commonly bite, such as cows, sheep and rabbits. This hypothesis logically postulated that when an alpha-gal-laden tick bit a human, the tick injected the human with alpha-gal, thus inducing the production of anti-alpha-gal IgE antibodies. This hypothesis implies that tick larvae that have never previously been fed on animals cannot induce alpha-gal syndrome. Alejandro Cabezas-Cruz and his colleagues from the BIPAR JRU (ANSES, EnvA, INRAE), based at the ANSES Animal Health Laboratory (Maisons-Alfort) and from Spain, wondered whether ticks could not produce their own alpha-gal, calling this hypothesis into question. In a manuscript published in the journal Scientific Reports (https://rdcu.be/7mlF), Alejandro Cabezas-Cruz described the discovery of three tick genes encoding galactosyl transferase enzymes capable of producing alpha-gal. When human and bacterial cells that do not naturally produce alpha-gal were transformed with these genes, the alpha-gal-negative cells became alpha-gal-positive. Furthermore, when these genes were inhibited by RNA interference, alpha-gal levels in the ticks decreased. The researchers also showed that the pathogenic bacterium transmitted by ticks, Anaplasma phagocytophilum, induces the expression of one of these genes, leading to an increase in alpha-gal in the ticks.

This study has two main implications. Firstly, it shows that ticks do not need to feed on an animal to acquire alpha-gal. Consequently, the bite of any tick stage, including larvae, can induce alpha-gal syndrome. Secondly, ticks infected with the bacterium Anaplasma phagocytophilum may have higher levels of alpha-gal, increasing the likelihood of inducing alpha-gal syndrome. This sheds new light on the interactions between ticks and the microbial agents they can transmit, since the consequences of this microbial infection of ticks may not only be the transmission of pathogenic agents to animals and/or humans, but also an increased ability of infected ticks to induce an allergic syndrome in humans.