Brucella abortus RNA inhibits the expression of major histocompatibility complex class I (MHCI) molecules in human monocytes

MILILLO M. A., VELASQUEZ L. N., DELPINO, M. V., GIAMBARTOLOMEI G. H.; BARRIONUEVO P

Congreso; LXII Reunión Científica de la Sociedad Argentina de Inmunología; 2014

Brucella abortus 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-γ-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 class of viability-associated PAMPs (vita-PAMPs). Thus, the aim of this study was to evaluate the effect of B. abortus RNA on IFN-γ-induced MHC-I expression. For this, human monocytic THP-1 cells were incubated with B. abortus RNA (0.1-20 µg/ml) in the presence of IFN-γ 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-γ-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 of MHC-I molecules observed with the infection. Interestingly, significant MHC-I down-regulation (p<0.05) was obtained with Salmonella typhimurium and Escherichia coli 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+ T cell immunological surveillance establishing a chronic infection