B cell-deficient mice display markedly enhanced resistance to the intracellular bacterium Brucella abortus.

摘要

BACKGROUND: Brucella species are facultative intracellular bacteria that cause lifelong infections in humans and livestock. METHODS: Here we evaluated the contribution of B cells in control of murine brucellosis in the more susceptible BALB/c and the more resistant C57BL/6 mice by infecting B cell-deficient mice. RESULTS: Strikingly, in the absence of B cells in both C57BL/6 and BALB/c mice, 99% and 99.5% of the infection found in wild type mice was cleared, respectively. This augmented clearance was not reversed in either strain by passive transfer of immune serum. In C57BL/6 mice, the clearance of infection coincided with an increase in interferon gamma (IFN-gamma)-producing CD4 and CD8 T cells and a reduction in interleukin 10 (IL-10)-producing cells. In BALB/c mice, this clearance was IFN-gamma-dependent, as B cell/IFN-gamma dual knockout mice were unable to clear the infection, and was inversely related to the levels of transforming growth factor beta (TGF-beta). Furthermore, B cells were found to produce TGF-beta and IL-10 during early stages of infection in BALB/c wild-type and C57BL/6 wild-type mice, respectively. CONCLUSIONS: Thus, we demonstrate that the establishment of the high plateau phase of infection is dependent on non-antibody-mediated B cell effector mechanisms, including B regulatory functions, during murine brucellosis.