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

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.

Vaccination with Alpha-Gal Protects Against Mycobacterial Infection in the Zebrafish Model of Tuberculosis

“…Then, results in leishmaniasis and Chagas disease further supported this possibility [18][19][20], leading to proposing the possibility of development of a single-antigen pan-vaccine for the control of major infectious diseases worldwide [11,16,17,30]. Pathogens causing infectious diseases with high incidence worldwide and with α-Gal modifications include Plasmodium, Mycobacterium, Leishmania, Trypanosoma, Anaplasma, Borrelia, and Aspergillus species and viruses such as human immunodeficiency virus (HIV), measles virus, vaccinia virus, paramyxovirus, vesicular stomatitis virus, Sindbis virus, and retroviruses [6,9,14,15,[17][18][19][20][21].…”

“…Within the conflict and cooperation that drove the evolution of tick-host-pathogen interactions [13], humans evolved by losing the capacity to synthesize α-Gal to increase the protective immune response against pathogens with this modification on their surface while increasing the risk to develop the AGS [6]. This evolutionary adaptation suggested the possibility of developing vaccines and other interventions to induce the anti-α-Gal IgM/IgG protective response against pathogen infection to prevent or control major infectious diseases worldwide [14][15][16][17][18][19][20].…”

Gut Microbiota Abrogates Anti-α-Gal IgA Response in Lungs and Protects against Experimental Aspergillus Infection in Poultry

“…The detection of α-Gal by flow cytometry was performed as previously described [20,24]. Briefly, samples were analyzed on a FACSCalibur flow cytometer equipped with CellQuest Pro software (BD Bio-Sciences, Madrid, Spain).…”

“…Aspergillosis, produced by the saprophytic opportunist fungus Aspergillus fumigatus with α-Gal on its surface [24], is one of the most prevalent airborne fungal infections affecting humans and animals worldwide [25][26][27]. Aspergillus fumigatus can cause a life-threatening disease in immunosuppressed and vulnerable individuals.…”

“…In humans, acute aspergillosis emerges as one of the first medical concerns in immunocompromised patients, especially those submitted to bone marrow or solid-organ transplantation or patients with cancer or HIV [25,27]. Despite the infective stage of A. fumigatus, the conidia, expresses high levels of α-Gal on its outer wall and the epitope is exposed to the host immune system; no difference in the levels of circulating anti-α-Gal IgG, IgM and IgE was found in patients with invasive aspergillosis and healthy control individuals [24]. In animals, vulnerability to Aspergillus infection varies among host species, with birds exhibiting the highest susceptibility.…”