Using a murine model of Alpha-gal syndrome to study tick bite-induced immune responses

The development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to cause a red meat allergy. Alpha-Gal Syndrome (AGS) has gained significant attention globally due to its increasing prevalence, with more than 450,000 cases in the United States. Previous research has established a connection between AGS and tick bites, which sensitize individuals to α-gal antigens and elevate specific IgE. However, the mechanism by which tick bites influence the host’s immune system and contribute to the development of AGS remains poorly investigated. This study investigated various factors related to ticks and host-associated with AGS development, following a tick bite, using mice with targeted disruption of alpha-1,3-galactosyltransferase (AGKO) as a model organism. Amblyomma americanum nymphs were used to sensitize AGKO mice, followed by pork meat challenge. Antibody responses in sensitized mice were determined. Tick bite site biopsies from sensitized and non-sensitized mice were subjected to mRNA gene expression analysis to assess host immune response. Our results showed a significant increase in the total IgE, IgG1, and α-gal IgG1 antibodies titers in the tick-sensitized AGKP mice. Pork challenge in tick-sensitized mice resulted in a decline in body temperature, and gene expression analysis revealed that tick bites direct mouse immunity toward Th2 and host sensitization to the α-gal antigen. This study supports the hypothesis that specific tick species may increase the risk of α-gal IgE and hypersensitivity to AGS, providing opportunities for future research on the mechanistic role of tick and host-related factors in AGS development.