title: Brucella abortus induces intracellular retention of MHC-I molecules in human macrophages down-modulating cytotoxic CD8(+) T cell responses.
abstract: 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.
authors.affiliation: Instituto de Estudios de la Inmunidad Humoral (CONICET/UBA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires (UBA), Buenos Aires, Argentina; Instituto de Inmunología, Genética y Metabolismo, Hospital de Clínicas 'José de San Martín', (CONICET/UBA), Buenos Aires, Argentina.
authors.forename: Paula
authors.initials: P
authors.lastname: Barrionuevo
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Delpino
authors.forename: Roberto G
authors.initials: RG
authors.lastname: Pozner
authors.forename: Lis N
authors.initials: LN
authors.lastname: Velásquez
authors.forename: Juliana
authors.initials: J
authors.lastname: Cassataro
authors.forename: Guillermo H
authors.initials: GH
authors.lastname: Giambartolomei
mesh_terms: D002003:Brucella abortus / Q000276:immunology* / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D006056:Golgi Apparatus / Q000737:chemistry; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D021381:Protein Transport
chemical_list: D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma