C57BL/6 α1,3-galactosyltransferase Knockout Mouse (α-GalT-KO) as an Animal Model for Experimental Chagas Disease.

The leading animal model of experimental Chagas disease, the mouse, plays a significant role in studies for vaccine development, diagnosis, and human therapies. Humans, along with Old World primates, alone among mammals, cannot make the terminal carbohydrate linkage of the α-Gal trisaccharide. It has been established that the anti-α-Gal immune response is likely to be a critical factor for protection against T. cruzi infection in humans. However, the mice customarily employed for the study of T. cruzi infection naturally express the α-Gal epitope and therefore, does not produce anti-α-Gal antibodies. Here we used the C57BL/6 α1,3-galactosyltransferase knockout mouse (α-GalT-KO), which does not express the α-Gal epitope as a model for experimental Chagas disease. We found the anti-α-Gal IgG antibody response to an increase in α-GalT-KO mice infected with Arequipa and Colombiana strains of T. cruzi, leading to fewer parasite nests, lower parasitemia, and an increase of INF-γ, TNF-α, and IL-12 cytokines in the heart of α-GalT-KO compared with α-GalT-WT mice, on days 60 and 120 post-infection. We, therefore, agree that the C57BL/6 α-GalT-KO mouse represents a superior model for initial testing of therapeutic and immunological approaches against different strains of T. cruzi.