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

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. A vexing enigma of Brucella immunity is its long‐term persistence in the host despite a vigorous and specific immune response. Our study describes a novel immune evasion mechanism whereby B. abortus down‐modulates the expression of IFN‐γ‐induced MHC‐I molecules in the surface of infected macrophages by sequestering them within the Golgi apparatus which correlates with a diminished CD8+ cytotoxic T cell response. These results provide new insights about how B. abortus is able to persist in its hosts in the presence of immune CD8+ T cells, establishing a chronic infection.