Abstract
α-Gal syndrome (AGS) is a type of anaphylactic reaction to mammalian meat characterized by an immunoglobulin (Ig)E immune response to the oligosaccharide α-Gal (Galα1-3Galβ1-4GlcNAc-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 α-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 α-Gal. For this, different developmental stages of the infectious agents were tested for the presence of α-Gal. Next, the potential correlation between immune responses to α-Gal and the parasite infections was investigated by testing sera collected from patients with AGS and those infected with the parasites. Our results showed that S. mansoni and A. fumigatus produce the terminal α-Gal moieties, but they were not able to induce the production of specific antibodies. By contrast, T. canis, A. suum and T. gondii lack the α-Gal epitope. Furthermore, the patients with T. canis infection had significantly decreased anti-α-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 α-Gal and parasitic infections. However, further investigations should be undertaken to identify T. canis components with potent immunomodulatory properties and to assess their potential to be used in immunotherapy and control of AGS.
Highlights
The α-Gal epitope (Galα1-3Galβ1-4GlcNAc-R) is an oligosaccharide ubiquitously present on glycoproteins and glycolipids of non-primate mammals, prosimians, and New World monkeys [1].In these mammals, the glycosylation enzyme α-1,3-galactosyltransferase (α1,3GT) catalyzes the synthesis of the glycan molecule by transferring galactose from uridine diphosphate (UDP)-Gal toN-acetyllactosaminide [2]
To assess the potential of the tested organisms to induce an immune response to α-Gal in humans, we investigated the presence of α-Gal epitopes on glycoproteins of adult worms and larval excretory/secretory antigens (ES) products, as well as on the surface of the developmental stages of helminth and protozoan parasites and parasitic fungi. α-Gal production was detected using the highly specific mouse anti-α-Gal antibody (mAb) M86 that recognizes synthetic and naturally produced terminal α-Gal epitopes, in particular, the α1-3 linkage on different glycoproteins and glycolipids [49]
The synthetic Galα1-3Gal-human serum albumin (HSA) epitope could be detected with the M86 mAb in both Western blot
Summary
The α-Gal epitope (Galα1-3Galβ1-4GlcNAc-R) is an oligosaccharide ubiquitously present on glycoproteins and glycolipids of non-primate mammals, prosimians, and New World monkeys [1].In these mammals, the glycosylation enzyme α-1,3-galactosyltransferase (α1,3GT) catalyzes the synthesis of the glycan molecule by transferring galactose from uridine diphosphate (UDP)-Gal toN-acetyllactosaminide [2]. Humans and ancestral anthropoid primates lack the capacity to produce the α-Gal epitope due to the functional disruption of the α1,3GT gene, caused by several deletions in the DNA sequence that encodes premature stop codons [3,4]. This unique evolutionary event resulted in a complete loss of immune tolerance to the α-Gal epitope and the consequent ability of all immunocompetent crown catarrhines to generate a large amount of anti-α-Gal antibodies (Abs) [5,6]. The resulting IgG and IgM Abs were found to be protective against important microbial and parasitic infections [8,9,10,11]
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