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

  • Edward Valencia Ayala
    Edward Valencia Ayala
    Laboratório de Imunologia e Genômica de Parasitos, Departamento de Parasitologia, Instituto de Ciências Biológicas/ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270901, Brazil
    Instituto de Investigación, Centro de Investigación en Inmunología e Infectología, Facultad de Medicina Humana, Universidad de San Martin de Porres, Lima 15000, Perú
  • Gisele Rodrigues da Cunha
    Gisele Rodrigues da Cunha
    Laboratório de Imuno-Proteômica e Biologia de Parasitos, Departamento de Parasitologia, Instituto de Ciências Biológicas/ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270901, Brazil
  • Maira Araujo Azevedo
    Maira Araujo Azevedo
    Laboratório de Imuno-Proteômica e Biologia de Parasitos, Departamento de Parasitologia, Instituto de Ciências Biológicas/ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270901, Brazil
  • Maritza Calderon
    Maritza Calderon
    Laboratorio de Investigación en Enfermedades Infecciosas and Laboratorio de Biología Molecular, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 15000, Perú
  • Juan Jimenez
    Juan Jimenez
    Laboratorio de Parasitología en Fauna Silvestre y Zoonosis, Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Lima 15000, Perú
    More by Juan Jimenez
  • Ana Paula Venuto
    Ana Paula Venuto
    Laboratório de Imuno-Proteômica e Biologia de Parasitos, Departamento de Parasitologia, Instituto de Ciências Biológicas/ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270901, Brazil
  • Ricardo Gazzinelli
    Ricardo Gazzinelli
    Instituto de Pesquisa Rene Rachou, Fundacao Oswaldo Cruz, Belo Horizonte, Minas Gerais 30190-009, Brazil
    Plataforma de Medicina Translacional, Fundacao Oswaldo Cruz, Belo Horizonte, Minas Gerais 30190-009, Brazil
  • Raúl Jesus Ynocente Lavalle
    Raúl Jesus Ynocente Lavalle
    Laboratorio de Parasitología en Fauna Silvestre y Zoonosis, Facultad de Ciencias Biológicas, Universidad Nacional Mayor de San Marcos, Lima 15000, Perú
  • Angela Giovana Vidal Riva
    Angela Giovana Vidal Riva
    Instituto de Investigación, Centro de Investigación en Inmunología e Infectología, Facultad de Medicina Humana, Universidad de San Martin de Porres, Lima 15000, Perú
    Laboratorio de Investigación en Enfermedades Infecciosas and Laboratorio de Biología Molecular, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima 15000, Perú
  • Robert Hincapie
    Robert Hincapie
    School of Chemistry and Biochemistry, School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia 30332 United States
  • M. G. Finn
    M. G. Finn
    School of Chemistry and Biochemistry, School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia 30332 United States
    More by M. G. Finn
  • , and 
  • Alexandre F. Marques*
    Alexandre F. Marques
    Laboratório de Imuno-Proteômica e Biologia de Parasitos, Departamento de Parasitologia, Instituto de Ciências Biológicas/ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270901, Brazil
    *Email: [email protected] or [email protected]
Cite this: ACS Infect. Dis. 2020, 6, 7, 1807–1815
Publication Date (Web):May 6, 2020
https://doi.org/10.1021/acsinfecdis.0c00061
Copyright © 2020 American Chemical Society

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    Abstract

    Abstract Image

    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-γ, 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.

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    Cited By

    This article is cited by 6 publications.

    1. Manu De Rycker, Susan Wyllie, David Horn, Kevin D. Read, Ian H. Gilbert. Anti-trypanosomatid drug discovery: progress and challenges. Nature Reviews Microbiology 2023, 21 (1) , 35-50. https://doi.org/10.1038/s41579-022-00777-y
    2. Juan Carlos Gabaldón-Figueira, Nieves Martinez-Peinado, Elisa Escabia, Albert Ros-Lucas, Eric Chatelain, Ivan Scandale, Joaquim Gascon, María-Jesús Pinazo, Julio Alonso-Padilla. State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation. Research and Reports in Tropical Medicine 2023, Volume 14 , 1-19. https://doi.org/10.2147/RRTM.S415273
    3. Léo Boussamet, Emmanuel Montassier, Jean-Paul Soulillou, Laureline Berthelot. Anti α1-3Gal antibodies and Gal content in gut microbiota in immune disorders and multiple sclerosis. Clinical Immunology 2022, 235 , 108693. https://doi.org/10.1016/j.clim.2021.108693
    4. Rita Vaz-Rodrigues, Lorena Mazuecos, José de la Fuente. Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS). Journal of Asthma and Allergy 2022, Volume 15 , 957-970. https://doi.org/10.2147/JAA.S265660
    5. Kira Dobrochaeva, Nailya Khasbiullina, Nadezhda Shilova, Yuriy Knirel, Polina Obukhova, Alexey Nokel, Roman Kunetskiy, Svetlana Tsygankova, Daniel Bello‐Gil, Cristina Costa, Rafael Mañez, Nicolai Bovin. Specificity profile of αGal antibodies in αGalT KO mice as probed with comprehensive printed glycan array: Comparison with human anti‐Galili antibodies. Xenotransplantation 2021, 28 (3) https://doi.org/10.1111/xen.12672
    6. Miriam Hils, Florian Wölbing, Christiane Hilger, Jörg Fischer, Nils Hoffard, Tilo Biedermann. The History of Carbohydrates in Type I Allergy. Frontiers in Immunology 2020, 11 https://doi.org/10.3389/fimmu.2020.586924

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