Open AccessB rucella abortus induces intracellular retention of MHC ‐ I molecules in human macrophages down‐modulating cytotoxic CD8 + T cell responses
Author(s) -
Barrionuevo Paula,
Delpino M. Victoria,
Pozner Roberto G.,
Velásquez Lis N.,
Cassataro Juliana,
Giambartolomei Guillermo H.
Publication year - 2013
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12058
Subject(s) - cytotoxic t cell , biology , cd8 , major histocompatibility complex , mhc class i , microbiology and biotechnology , intracellular , t cell , immune system , immunology , biochemistry , in vitro
Summary B rucella 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 CD 107a 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 G olgi 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.