Brucella abortus induces intracellular retention of MHC-I molecules in human macrophages down-modulating cytotoxic CD8+ T cell responses

Authors

  • Paula Barrionuevo,

    1. Instituto de Estudios de la Inmunidad Humoral (CONICET/UBA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
    2. Instituto de Inmunología, Genética y Metabolismo, Hospital de Clínicas ‘José de San Martín’, (CONICET/UBA), Buenos Aires, Argentina
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  • M. Victoria Delpino,

    1. Instituto de Estudios de la Inmunidad Humoral (CONICET/UBA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
    2. Instituto de Inmunología, Genética y Metabolismo, Hospital de Clínicas ‘José de San Martín’, (CONICET/UBA), Buenos Aires, Argentina
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  • Roberto G. Pozner,

    1. Instituto de Medicina Experimental (CONICET-Academia Nacional de Medicina), Buenos Aires, Argentina
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  • Lis N. Velásquez,

    1. Instituto de Estudios de la Inmunidad Humoral (CONICET/UBA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
    2. Instituto de Inmunología, Genética y Metabolismo, Hospital de Clínicas ‘José de San Martín’, (CONICET/UBA), Buenos Aires, Argentina
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  • Juliana Cassataro,

    1. Instituto de Estudios de la Inmunidad Humoral (CONICET/UBA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
    2. Instituto de Inmunología, Genética y Metabolismo, Hospital de Clínicas ‘José de San Martín’, (CONICET/UBA), Buenos Aires, Argentina
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  • Guillermo H. Giambartolomei

    Corresponding author
    1. Instituto de Inmunología, Genética y Metabolismo, Hospital de Clínicas ‘José de San Martín’, (CONICET/UBA), Buenos Aires, Argentina
    • Instituto de Estudios de la Inmunidad Humoral (CONICET/UBA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
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For correspondence. E-mail ggiambart@ffyb.uba.ar; Tel. (+54) 11 5950 8755; Fax (+54) 11 5950 8758.

Summary

Brucella abortus elicits a vigorous Th1 immune response which activates cytotoxic T lymphocytes. However, B. abortus persists in its hosts in the presence of CD8+ T cells, establishing a chronic infection. Here, we report that B. abortus infection of human monocytes/macrophages inhibited the IFN-γ-induced MHC-I cell surface expression. This phenomenon was dependent on metabolically active viable bacteria. MHC-I down-modulation correlated with the development of diminished CD8+ cytotoxic T cell response as evidenced by the reduced expression of the activation marker CD107a on CD8+ T lymphocytes and a diminished percentage of IFN-γ-producing CD8+ T cells. Inhibition of MHC-I expression was not due to changes in protein synthesis. Rather, we observed that upon B. abortus infection MHC-I molecules were retained within the Golgi apparatus. Overall, these results describe a novel mechanism based on the intracellular sequestration of MHC-I molecules whereby B. abortus would avoid CD8+ cytotoxic T cell responses, evading their immunological surveillance.

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