Cytotoxic T cell epitope in Brucellosis-induced murine spondyloarthropathy shows 100% homology with the host mouse peptide (160.6)

Abstract

Abstract Brucellosis is resulted in spondyloarthropathy (SpA) in almost 50% of human patients, but mechanisms of this association are poorly characterized. To study immune mechanisms of SpA, BALB/c mice were infected with bioluminescent B.melitensis, and bacterial dissemination in spleen, liver and axial skeleton was monitored using bioluminescence and immunohistochemistry (IHC). At the peak of infection, bioluminescence showed accumulation of bacteria in front and hind paws, but the strongest signal was detected in the caudal skeleton reproducing the distribution of vertebrae. IHC confirmed intracellular bacteria in spleen, liver, and in the subchondral bone marrow of vertebrae and in peripheral joints without inflammatory cells infiltration. At 26 weeks post infection, bacteria were cleared from the body, but mice developed ankle joint arthritis and spondylolisthesis. We found that immunodominant Brucella-derived peptide from methionine sulfoxide reductase is presented by murine macrophages in context of MHC class I molecule to cytotoxic T cells (CTL). Homologous mouse/host protein carries a sequence that is 100% identical to Brucella epitope. In silico prediction analysis indicates that Brucella epitope binds to human HLA-B*2705 and B*2702 class I molecules, that are strongly associated with human SpA. Our data provide support for brucellosis-induced SpA as a reactive arthritis-type disease with a potential involvement of CTL in the disease pathogenesis.