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

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.

Identification of Immune Effectors Essential to the Control of Primary and Secondary Intranasal Infection with Brucella melitensis in Mice

“…However, we observed that TCR-d and TAP1 deficiency, but not MHCII deficiency, also affected early Brucella control in the lungs, suggesting that these cells could be a potential source of IL-17A in our model. In keeping with this observation, IL-17 production by g/d T cells was reported in a Brucella model (65) and in several other pulmonary infectious models (66)(67)(68).…”

CCL25 induces α4β7 integrin‐dependent migration of IL‐17+γδ T lymphocytes during an allergic reaction

“…The role of IL-17 + γδ T lymphocytes (and of IL-17) in infection, tumor immunity, and autoimmunity has been reported, and it is still controversial [50,[58][59][60][61][62][63]. A clear involvement of IL-17 + γδ T lymphocytes in autoimmunity has been evidenced in experimental arthritis and autoimmune encephalomyelitis, in which these cells have been shown to amplify CD4 + Th17 cell responses, to suppress Foxp3 + Treg cells, and to contribute to the development of the response [48,[62][63][64].…”

“…Therefore, it is possible that the relevance of CCL25 in the context of allergic responses is correlated to IL-17 production in the allergic site. Whether this phenomenon contributes to the enhancement or regulation of allergy is still unclear, since contrasting roles for IL-17 have been described [54][55][56][57].The role of IL-17 + γδ T lymphocytes (and of IL-17) in infection, tumor immunity, and autoimmunity has been reported, and it is still controversial [50,[58][59][60][61][62][63]. A clear involvement of IL-17 + γδ T lymphocytes in autoimmunity has been evidenced in experimental arthritis and autoimmune encephalomyelitis, in which these cells .…”

Gamma-Delta T-Cell Responses During SubcutaneousMycobacterium aviumSubspeciesparatuberculosisChallenge in Sensitized or Naïve Calves Using Matrix Biopolymers

“…Early production of IFNg for activation of other T cells, dendritic cells, and macrophages is known to be a critical step during early host defense against pathogens and in particular against invading intracellular agents. 14,29 More work is needed to clarify the mechanisms of gd T-cell recruitment to and activation at infection sites and what potential roles they may play during development of adaptive immunity. This research represents an initial step toward potential identification of key factors mediating either success or failure of host immunity during intracellular infections and ultimately leading to pathogen clearance/healing or establishment of persistent infection, respectively.…”