IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Brucella abortus induces intracellular retention of MHC-I molecules in human macrophages down-modulating cytotoxic CD8+ T cell responses.
Autor/es:
BARRIONUEVO PAULA; DELPINO M. VICTORIA; POZNER ROBERTO; VELAZQUEZ LIS; CASSATARO JULIANA; GIAMBARTOLOMEI GUILLERMO H.
Revista:
CELLULAR MICROBIOLOGY (PRINT)
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2013 p. 487 - 502
ISSN:
1462-5814
Resumen:
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.