Background Brucellosis is one of the most common bacterial zoonosis and causes significant human morbidity worldwide1. Osteoarticular complications are the most frequent clinical manifestations in patients2,3. However, pathophysiological and immune mechanisms of brucellosis remain poorly characterized.
Objectives The goal of the study was to establish a murine model for human Brucellosis to better understanding the immune mechanisms of association between Brucellosis and spondyloarthropathy (SpA).
Methods BALB/c mice were infected intraperitoneally with 106–108 CFU of the virulent bioluminescent B. melitensis strain GR023 or B. abortus vaccine strain S194,5. Bacterial dissemination was monitored using biophotonic imaging and immunohistochemistry (IHC). Histopathology slides of axial skeleton, paws, spleen, and liver were IHC stained for IBA-1 marker and Brucella.
Results In vivo biophotonic imaging showed accumulation of B.melitensis in paws and knees, while the strongest signal was detected in the tail that reproduce the distribution of vertebrae. Upon IHC staining, bacteria were found in the spleen, liver, and in bone marrow. Three weeks post-infection, bacteria-infected cells were not found in the peridiscal space or in the joint cavity, but were located in the subchondral bone of peripheral joints and vertebrae. At 26 weeks post-infection, spleen and bone marrow were negative for IHC staining, and liver showed a weak rare staining. Despite the general absence of infection at this time point, mice developed arthritis in ankle joints and spondylolisthesis.
We found that immunodominant Brucella-derived peptide from methionine sulfoxide reductase is presented to cytotoxic T cells by murine macrophages in the context of MHC class I molecule. Homologous mouse/host protein carries a sequence that is 100% identical to Brucella epitope. In silico prediction analysis indicates that the epitope is able to bind to human HLA-B*2705 class I molecule that is strongly associated with human SpA.
Conclusions Arthritis was not associated with acute Brucella infection in this murine model. Inflammation in joints and changes in skeleton were found weeks after the bacteria were cleared from tissues. Murine Brucellosis demonstrated features that are typical to reactive arthritis. Our data provide support for brucellosis-induced SpA as a reactive arthritis-type disease with a potential involvement of cytotoxic T cells.
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Disclosure of Interest None Declared
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