Abstract
γδ 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 γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ−/− 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 TCRγδ 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. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα−/−, and GMCSF−/− mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ−/− mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ 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-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections.
Highlights
Brucellosis is a widespread and economically important agricultural and human disease in many regions of the world
The pathological manifestations of brucellosis are diverse, depending upon host, and in humans include arthritis, endocarditis, and meningitis, while animal brucellosis is characterized by spontaneous abortions [2]
To assess the role of cd T cells in protection against brucellosis, TCRd2/2 and wild-type C57BL/6 mice were infected with B. abortus, and at select time points (1, 3, 7, 14, 21, and 28 days postinfection), the extent of splenic colonization was determined (Figure 1A)
Summary
Brucellosis is a widespread and economically important agricultural and human disease in many regions of the world. The pathological manifestations of brucellosis are diverse, depending upon host, and in humans include arthritis, endocarditis, and meningitis, while animal brucellosis is characterized by spontaneous abortions [2]. Use of the B. abortus vaccine strains S19 and RB51 reduces disease incidence and prevents B. abortus-induced abortions, these vaccines are less than ideal because of their limited efficacy and potential to cause disease in humans [3,4]. The need exists for improved animal protective measures that will combine safety and efficacy to all species at risk, including domestic herds and wildlife [5]. The need exists to determine protective innate immune responses against brucellosis to lessen the progression of infection and to allow a protective, adaptive immune response to develop [6]
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