期刊
ACS INFECTIOUS DISEASES
卷 6, 期 7, 页码 1807-1815出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsinfecdis.0c00061
关键词
Chagas disease; alpha-Gal; mouse model; Trypanosoma cruzi; alpha-Gal antibodies; alpha-Gal knockout mouse
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [407926/2018-6]
- Conselho Nacional de Desenvolvimento de Pesquisa e Tecnologia (CNPq) [465293/2014-0]
- Georgia Institute of Technology
- National Institutes of Health [R01 CA149451]
- National Institute of Science and Technology on Vaccines
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 alpha-Gal trisaccharide. It has been established that the anti-alpha-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 alpha-Gal epitope and therefore do not produce anti-alpha-Gal antibodies. Here, we used the C57BL/6 alpha-1,3-galactosyltransferase knockout (alpha-GaIT-KO) mouse, which does not express the alpha-Gal epitope as a model for experimental Chagas disease. We found the anti-alpha-Gal IgG antibody response to an increase in alpha-GaIT-KO mice infected with Arequipa and Colombiana strains of T. cruzi, leading to fewer parasite nests, lower parasitemia, and an increase of INF-gamma, TNF-alpha, and IL-12 cytokines in the heart of alpha-GaIT-KO mice compared with alpha-GaIT-WT mice on days 60 and 120 postinfection. We therefore agree that the C57BL/6 alpha-GaIT-KO mouse represents a useful model for initial testing of therapeutic and immunological approaches against different strains of T. cruzi.
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