Murine and Bovine γδ T Cells Enhance Innate Immunity against Brucella abortus Infections

gamma delta T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human gamma delta T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of gamma delta T cells in vivo during experimental brucellosis has not been studied. Here we report TCR delta(-/-) mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCR gamma delta cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. gamma delta T cells were the major source of IL-17 following infection and also produced IFN-gamma. Depletion of gamma delta T cells from C57BL/6, IL-17R alpha(-/-), and GMCSF(-/-) mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when gamma delta T cells were depleted from IFN-gamma(-/-) mice, enhanced susceptibility was observed. Neutralization of gamma delta T cells in the absence of TNF-alpha did not further impair immunity. In the absence of TNF-alpha or gamma delta T cells, B. abortus-infected mice showed enhanced IFN-gamma, suggesting that they augmented production to compensate for the loss of gamma delta T cells and/or TNF-alpha. While the protective role of gamma delta T cells was TNF-alpha-dependent, gamma delta T cells were not the major source of TNF-alpha and activation of gamma delta T cells following B. abortus infection was TNF-alpha-independent. Additionally, bovine TCR gamma delta cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-gamma. Collectively, these results demonstrate gamma delta T cells are important for early protection to B. abortus infections.