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.
Bibliographical noteFunding Information:
This work was supported in part by the Conselho Nacional de Desenvolvimento Cientifico e Tecnológico (CNPQ no. 407926/2018-6), the National Institute of Science and Technology on Vaccines, Conselho Nacional de Desenvolvimento de Pesquisa e Tecnologia (CNPq, 465293/2014-0), and the Georgia Institute of Technology and the National Institutes of Health (R01 CA149451).
Copyright © 2020 American Chemical Society.
- Chagas disease
- Trypanosoma cruzi
- mouse model
- α-Gal antibodies
- α-Gal knockout mouse