Brucella abortus induces intracellular retention of MHC‐I molecules in human macrophages down‐modulating cytotoxic CD8+ T cell responses. (21st November 2012)

• Record Type: Journal Article
• Authors: Barrionuevo, Paula; Delpino, M. Victoria; Pozner, Roberto G.; Velásquez, Lis N.; Cassataro, Juliana; Giambartolomei, Guillermo H.
• Is Part Of: Cellular microbiology. Volume 15:Number 4(2013:Apr.)
• Page Start: 487
• Page End: 502
• Publication Date: 2012-11-21
• Subjects: Microbiology -- Periodicals; Cytology -- Periodicals; Host-parasite relationships -- Periodicals; Microbiology -- Periodicals; Cells -- Periodicals; Microbiologie -- Périodiques; Microbiologie; Relation hôte-parasite; Cytologie; Cellule; Réponse cellulaire; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); 579.05
• DOI: 10.1111/cmi.12058
• Languages: English
• ISSNs: 1462-5814

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>Brucella abortus</italic> elicits a vigorous Th1 immune response which activates cytotoxic T lymphocytes. However, <italic>B. abortus</italic> persists in its hosts in the presence of CD8⁺ T cells, establishing a chronic infection. Here, we report that <italic>B. abortus</italic> 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 <italic>B. abortus</italic> 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 <italic>B. abortus</italic> would avoid CD8⁺ cytotoxic T cell responses, evading their immunological surveillance.</p> </abstract>