C57BL/6 α-1,3-Galactosyltransferase Knockout Mouse as an Animal Model for Experimental Chagas Disease

Ayala E.V.; Rodrigues Da Cunha G.; Azevedo M.A.; Calderon M.; Jimenez J.; Venuto A.P.; Gazzinelli R.; Lavalle R.J.Y.; Riva A.G.V.; Hincapie R.; Finn M.G.; Marques A.F. · ACS Infectious Diseases (2020) · DOI: 10.1021/acsinfecdis.0c00061

Resumen

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 Trypanosoma cruzi (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 do not produce anti-α-Gal antibodies. Here, we used the C57BL/6 α-1,3-galactosyltransferase knockout (α-GalT-KO) mouse, 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-Î, TNF-α, and IL-12 cytokines in the heart of α-GalT-KO mice compared with α-GalT-WT mice on days 60 and 120 postinfection. We therefore agree that the C57BL/6 α-GalT-KO mouse represents a useful model for initial testing of therapeutic and immunological approaches against different strains of T. cruzi. Copyright

Instituciones: Universidad Peruana Cayetano Heredia; Universidad Nacional Mayor de San Marcos; Universidad de San Martín de Porres