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-gamma (IFN-gamma) 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-gamma 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)-alpha and CD8 T cells were involved in controlling bacterial numbers in BALB/c mice during this time. That is, neutralization of TNF-alpha 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-alpha may depend upon the presence of interferon-gamma early in the infection since when TNF-alpha was neutralized in interferon-gamma gene knockout mice there was a marked increase in splenic macrophages, NK cells and neutrophils but not a significant increase in colony-forming units.

Role of Toll-Like Receptor 4 in Induction of Cell-Mediated Immunity and Resistance toBrucella abortusInfection in Mice

“…As with other intracellular microbial pathogens, IL-12-derived IFN-␥ production, and TNF-␣ are critical components of the immune system to control murine brucellosis (38,39). Our findings revealed that TLR4 is required for B. abortus LPS signaling to produce TNF-␣ and IL-12, while TLR2 is not.…”

“…Previous studies have demonstrated that B. abortus induces high levels of IFN-␥, TNF-␣, and IL-12 (38,39). Here, we tested the involvement of TLR2 and TLR4 on cytokine production by murine inflammatory macrophages stimulated with B. abortus S and R strains and their LPS.…”

Crucial Role of Gamma Interferon-Producing CD4+Th1 Cells but Dispensable Function of CD8+T Cell, B Cell, Th2, and Th17 Responses in the Control of Brucella melitensis Infection in Mice

“…The precise role of different components of adaptive immunity in the control of Brucella growth is quite controversial (1,3,6,24,48,51,52,55,58,60,61). Here, we compared the course of B. melitensis infection in the spleen of various C57BL/6 mice rendered genetically deficient for key elements of adaptive immune response: RAG (T and B cells),…”

“…ϩ T cells with anti-CD8␣ monoclonal antibodies (48,51,58) and using ␤ 2 -microglobulin-deficient (␤ 2 -microglobulin Ϫ/Ϫ ) mice (55). Both CD4 and CD8 T cells have been shown to be equally protective in adoptive transfer studies (1).…”

NFB is differentially activated in macrophages from J774A.1 cell line infected with vaccine or virulent strains of Brucella abortus

“…In turn, the role of TNF-α depends on the presence of IFN- during the first infection stages, as shown by neutralizing TNF-α in IFN- knockout mice that developed an inflammatory process in the spleen but did not reduce the number of CFU (Murphy et al, 2001a). As demonstrated in the present study, B. abortus RB51 induced the activation of the TNF-α gene in PEC, which was not achieved in mice infected with the virulent strain 2308.…”