Infection with Toxocara canis Inhibits the Production of IgE Antibodies to α-Gal in Humans: Towards a Conceptual Framework of the Hygiene Hypothesis?

alpha-Gal syndrome (AGS) is a type of anaphylactic reaction to mammalian meat characterized by an immunoglobulin (Ig)E immune response to the oligosaccharide alpha-Gal (Gal alpha 1-3Gal beta 1-4GlcNAc-R). Tick bites seems to be a prerequisite for the onset of the allergic disease in humans, but the implication of non-tick parasites in alpha-Gal sensitization has also been deliberated. In the present study, we therefore evaluated the capacity of helminths (Toxocara canis,Ascaris suum,Schistosoma mansoni), protozoa (Toxoplasma gondii), and parasitic fungi (Aspergillus fumigatus) to induce an immune response to alpha-Gal. For this, different developmental stages of the infectious agents were tested for the presence of alpha-Gal. Next, the potential correlation between immune responses to alpha-Gal and the parasite infections was investigated by testing sera collected from patients with AGS and those infected with the parasites. Our results showed thatS. mansoniandA. fumigatusproduce the terminal alpha-Gal moieties, but they were not able to induce the production of specific antibodies. By contrast,T. canis,A. suumandT. gondiilack the alpha-Gal epitope. Furthermore, the patients withT. canisinfection had significantly decreased anti-alpha-Gal IgE levels when compared to the healthy controls, suggesting the potential role of this nematode parasite in suppressing the allergic response to the glycan molecule. This rather intriguing observation is discussed in the context of the 'hygiene hypothesis'. Taken together, our study provides new insights into the relationships between immune responses to alpha-Gal and parasitic infections. However, further investigations should be undertaken to identifyT. caniscomponents with potent immunomodulatory properties and to assess their potential to be used in immunotherapy and control of AGS.