Immune control of Brucella abortus 2308 infections in BALB/c mice

Abstract BALB/c mice infected with Brucella abortus strain 2308 have 10-fold higher levels of bacteria during the plateau phase of infection (the time period when the number of colony-forming units in vivo remains consistent) than the more resistant C57BL/10 mice. This is due to a cessation of interferon-γ (IFN-γ) production that begins after the first week of infection and continues until the end of the plateau phase at least 6 weeks post infection. Despite the lack of IFN-γ production during this time BALB/c mice are able to prevent an increase in bacterial colony-forming units. Here it was shown that both tumor necrosis factor (TNF)-α and CD8 T cells were involved in controlling bacterial numbers in BALB/c mice during this time. That is, neutralization of TNF-α or depletion of CD8 T cells with monoclonal antibodies resulted in a significant increase in the number of splenic colony-forming units recovered at 3 weeks post infection. In the absence of CD8 T cells there was also a significant increase in splenic macrophages. The role of TNF-α may depend upon the presence of interferon-γ early in the infection since when TNF-α was neutralized in interferon-γ gene knockout mice there was a marked increase in splenic macrophages, NK cells and neutrophils but not a significant increase in colony-forming units.