BRUCELLA ABORTUS RNA INHIBITS THE EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I (MHC-I) MOLECULES IN HUMAN MONOCYTES

MILILLO AYELÉN; VELAZQUEZ LIS; DELPINO M. VICTORIA; GIAMBARTOLOMEI GUILLERMO H.; BARRIONUEVO PAULA

Congreso; LIX REUNIÓN CIENTÍFICA ANUAL Sociedad Argentina de Investigación Clínica LXII REUNIÓN ANUAL Sociedad Argentina de Inmunología; 2014

Brucella abortus elicits a vigorous Th1 immune responsewhich activates cytotoxic T lymphocytes. However, B. abortusis 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-Icell surface expression down-modulating cytotoxic CD8+ T cellresponses. MHC-I down-modulation depends on bacterial viabilityand results from the capacity of B. abortus to retain the MHC-Imolecules within the Golgi apparatus. However, the componentsof B. abortus involved in this phenomenon remained unknown.Prokaryotic RNA has been recently characterized as a class ofviability-associated PAMPs (vita-PAMPs). Thus, the aim of thisstudy was to evaluate the effect of B. abortus RNA on IFN-γ-induced MHC-I expression. For this, human monocytic THP-1cells were incubated with B. abortus RNA (0.1-20 μg/ml) in thepresence of IFN-γ for 48 h. The expression of MHC-I molecules(HLA-ABC) was then, evaluated by flow cytometry. B. abortusRNA significantly (p<0,05) down-regulated the IFN-γ-inducedsurface expression of MHC-I molecules in a dose-dependentfashion. Accordingly, when THP-1 cells were stimulated withheat-killed B. abortus or different structural components of thebacteria (lipoproteins, LPS or DNA), MHC-I down-modulation wasnot observed. By confocal microscopy, we also demonstratedthat B. abortus RNA mimics the intracellular retention of MHC-Imolecules observed with the infection. Interestingly, significantMHC-I down-regulation (p<0,05) was obtained with Salmonellatyphimurium and Escherichia coli RNAs but not with PBMCs RNA,indicating that the effect could be extended to other prokaryoticbut not eukaryotic RNAs. Overall, these results indicate thatthe vita-PAMP RNA is a component employed by B. abortus toinhibit MHC-I expression whereby the bacteria could evade thecytotoxic CD8+ T cell immunological surveillance establishing achronic infection.