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

Edward Valencia Ayala, Gisele Rodrigues Da Cunha, Maira Araujo Azevedo, Maritza Calderon, Juan Jimenez, Ana Paula Venuto, Ricardo Gazzinelli, Raúl Jesus Ynocente Lavalle, Angela Giovana Vidal Riva, Robert Hincapie, M. G. Finn, Alexandre F. Marques

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1807-1815
Number of pages9
JournalACS Infectious Diseases
Volume6
Issue number7
DOIs
StatePublished - 10 Jul 2020

Bibliographical note

Funding 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).

Publisher Copyright:
Copyright © 2020 American Chemical Society.

Keywords

  • Chagas disease
  • Trypanosoma cruzi
  • mouse model
  • α-Gal
  • α-Gal antibodies
  • α-Gal knockout mouse

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