INHIBITION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I (MHC-I) BY BRUCELLA ABORTUS IS AN EARLY EVENT DURING INFECTION AND INVOLVES THE EGF RECEPTOR PATHWAY

VELAZQUEZ LIS; DELPINO M. VICTORIA; MILILLO AYELÉN; 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 is able to persist inside the host despite thedevelopment of a potent CD8+ T cell response. We have recentlyreported the ability of B. abortus to inhibit the IFN-γ-induced cellsurface expression of MHC-I molecules on human monocytes.MHC-I down-modulation resulted in a diminished CD8+ cytotoxicT cell response and was dependent on bacterial viability. Theaim of this study was to further characterize this phenomenonby studying its kinetics and if it elicits a bystander effect. Forthis, THP-1 cells were infected with a virulent strain of B. abortus(S2308), a rough strain (RB51) or a mutant strain lacking the V irBType IV secretion system (virB10-) in the presence of IFN-γ for 48h. MHC-I expression was then evaluated by flow cytometry. All3 strains were able to diminish the IFN-γ-induced expression ofMHC-I molecules (p<0.05). However, only the S2308 strain wascapable of surviving intracellularly and establishing a successfulinfection. Thus, we evaluated the kinetics of MHC-I down-modulation.The phenomenon occurred early in time and was observableat 8 h post-infection (p<0.01). At 24 h and 48 h it was even morepronounced. Interestingly, even though few cells were infectedin culture, MHC-I down-regulation occurred in the whole population.Thus, we infected cells with B. abortus-GFP and evaluatedMHC-I expression in infected as well as non-infected cells. In bothpopulations MHC-I expression was inhibited (p<0.01). Moreover,supernants from B. abortus-infected cells were also able to inhibitMHC-I expression in non-infected THP-1 cells. Finally, neutrali zationof the EGF receptor by a monoclonal antibody (Cetuximab)resulted in partial recovery (p<0.01) of MHC-I expression indicatingthat EGF-like ligands may be the soluble mediators involved.Overall, these results describe how B. abortus evades CD8+ T cellresponses early during infection and generates a bystander effectto better escape from the immune system and favor chronicity.