What you need to know: Arthropod vector-borne diseases are a growing problem worldwide. Ticks are only second to mosquitoes as vectors of human diseases, and the most important vectors in animals. Recent evidence suggests that allergy to red meat consumption is associated with tick bites and emerging in America, Europe, Asia and Australia. Humans do not synthesize the carbohydrate α-Gal (Gal α 1-3Gal β 1-(3)4GlcNAc-R). Thus, all the sources of α-Gal for the human body are of non-human origin. This allows humans to develop a potent immune response against this carbohydrate. The IgG and IgM antibody (Ab) responses to α-Gal produced by some bacteria of the gut microbiota are beneficial as they protect against the transmission of vector-borne pathogens such as malaria parasites. However, the anti-α-Gal IgE Ab response triggered by tick salivary proteins inoculated into human body after tick bites is detrimental because it promotes the development of the Alpha-Gal Syndrome (AGS) characterized by anaphylactic reactions to tick bites, cetuximab, gelatin-containing substances and red meat. This suggests that while IgM and IgG to α-Gal can be protective against some pathogens, IgE to α-Gal might instead promote harmful allergies. Immunity to α-Gal provides a good model to study how Abs to α-Gal might promote allergy and/or protection against pathogen transmission by vectors. A strong argument for the existance of this trade-off is that individuals with blood type B produce fewer anti-α-Gal IgE Abs, and that AGS is strongly associated with blood type B negative individuals. The reduced capacity of blood group B individuals to produce anti-α-Gal Abs is presumably due to tolerance to α-Gal, which is similar to blood group B antigen.
Trade-off between allergy and protection to infectious diseases (α-Gal project)
Figure by Jindrǐch taken from (Trends Parasitol. 2017; 33(7):495-498)
In agreement with the negative effect of blood group B on anti-α-Gal immunity, the frequency of blood group B is positively correlated with the incidence of malaria in endemic regions. Understanding the balance between these two immune responses to α-Gal may lead to interventions to control both AGS and infectious diseases. Où on va? Currently, this project focuses on understanding the protective role of anti-α-Gal Abs in different models of bacterial, fungal and vector-borne bacterial infections. We also study the role of probiotic bacteria expressing α-Gal in the induction of an anti-α-Gal protective immunity. Our aim is to develop a 'probiotic-based single-antigen pan-vaccine to control major infectious diseases'
Figure by Alejandro taken from (ACS Cent Sci. 2017; 3(11):1140-1142)
We are also developing a model of AGS that we will use to test whether AGS is positively correlated with protection against infectious diseases.