IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Brucella RNA mimics the inhibition of Major Histocompatibility Complex class I (MHC-I) expression mediated by Brucella abortus on human monocytes.
Autor/es:
MILILLO MA; VELÁSQUEZ LN; DELPINO MV; POZNER RG; GIAMBARTOLOMEI GH; BARRIONUEVO P
Lugar:
Waterville Valley, NH
Reunión:
Congreso; Phagocytes Gordon Research Conference; 2015
Institución organizadora:
Gordon Research Conference
Resumen:
Brucella abortus is an intracellular Gram-negative bacterium that infects wild and domestic animals and can be transmitted to humans. Upon infection, Brucella elicits a vigorous Th1 immune response which activates cytotoxic T lymphocytes. However, B. abortus is able to persist inside its host and establishes a chronic infection. We recently reported that infection of human monocytes/macrophages with B. abortus inhibits the IFN-gamma-induced MHC-I cell surface expression down-modulating cytotoxic CD8+ T cell responses. MHC-I down-modulation depends on bacterial viability and results from the capacity of B. abortus to retain the MHC-I molecules within the Golgi apparatus. However, the components of B. abortus involved in this phenomenon remained unknown. Prokaryotic RNA has been recently characterized as a special class of viability-associated PAMPs (vita-PAMPs). Thus, the aim of this study was to evaluate the effect of B. abortus RNA on IFN-gamma-induced MHC-I expression on human monocytes. For this, THP-1 cells were incubated with B. abortus RNA (0.1-20 µg/ml) in the presence of IFN-gamma for 48 h. The expression of MHC-I molecules (HLA-ABC) was then evaluated by flow cytometry.B. abortus RNA significantly (p 0.05)down-regulated the IFN-gamma-induced surface expression of MHC-I molecules in a dose-dependent fashion.Accordingly, when THP-1 cells were stimulated with heat-killed B. abortus or different structural components of the bacteria (lipoproteins, LPS or DNA), MHC-I down-modulation was not observed. By confocal microscopy, we also demonstrated that B. abortus RNA mimics the intracellular retention within the Golgi apparatus of MHC-I molecules observed with the infection. Interestingly, significant MHC-I down-regulation (p 0.05) was obtained with Salmonella typhimurium and Bacillus cereus (Gram-negative and Gram-positive bacteria respectively) RNAs but not with PBMCs RNA, indicating that the effect could be extended to other prokaryotic but not eukaryotic RNAs. Overall, these results indicate that the vita-PAMP RNA is a component employed by B. abortus to inhibit MHC-I expression whereby the bacteria could evade the cytotoxic CD8+ Tcell immunological surveillance establishing a chronic infection.