Abstract
IL-17 has emerged as a key player in the immune system, exhibiting roles in protection from infectious diseases and promoting inflammation in autoimmunity. Initially thought to be CD4 T-cell-derived, the sources of IL-17 are now known to be varied and belong to both the innate and adaptive arms of the immune system. Mechanisms for inducing IL-17 production in lymphoid cells are thought to rely on appropriate antigenic stimulation in the context of TGF-β1, IL-6 and/or IL-1β. Using culture protocols adapted from human studies, we have effectively induced both bovine CD4+ and WC1+ γδ T-cells to produce IL-17 termed Th17 and γδ17 cells, respectively. The negative regulatory effect of IFN-γ on mouse and human IL-17 production can be extended to the bovine model, as addition of IFN-γ decreases IL-17 production in both cell types. Furthermore we show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a γδ17 phenotype that preferentially kills infected target cells. Our study identifies two T-cell sources of IL-17, and is the first to demonstrate a protective effect of IL-17+ T-cells in ruminants. Our findings offer further opportunities for future adjuvants or vaccines which could benefit from inducing these responses.
Highlights
Two distinct populations of Bovine IL-171 T-cells can be induced and WC11IL-171cd T-cells are effective killers of protozoan parasites
We show that infection with the protozoan Neospora caninum will induce fibroblasts to secrete pro-IL-17 factors thereby inducing a cd[17] phenotype that preferentially kills infected target cells
We have shown that these cells can be stimulated by supernatants collected from N. caninum-infected fibroblasts
Summary
Two distinct populations of Bovine IL-171 T-cells can be induced and WC11IL-171cd T-cells are effective killers of protozoan parasites. Studies have implicated IFN-c in pathology but others report conflicting results suggesting both a protective, preventing abortion[6], and a pathological, causing abortion, role[7,8] This leads us to hypothesize that a source(s) of IL-17 may have an important role in protection against foetal death and host tissue damage either in isolation or combination with other cytokines. We have recently shown that parasite limiting macrophages provoke IL-17 producing CD4 T-cells, with a Th17 phenotype equivalent to that seen in murine and human studies[10]. This is especially pertinent given the opposing effects that IL-17 and IFN-c can have on each other. Our hypothesis of IL-17 in protection against N. caninum and the abundance of cd T-cells in young cattle in comparison to other mammals[11], it was timely to investigate the ability of specific T-cell subsets to produce IL-17 and their functional relevance to protect against N. caninum infection
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