title: Two distinct populations of bovine IL-17⁺ T-cells can be induced and WC1⁺IL-17⁺γδ T-cells are effective killers of protozoan parasites.
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.
authors: School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, LE12 5RD.
authors: R K
authors: RK
authors: Peckham
authors: School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, LE12 5RD.
authors: R
authors: R
authors: Brill
authors: School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, LE12 5RD.
authors: D S
authors: DS
authors: Foster
authors: School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, LE12 5RD.
authors: A L
authors: AL
authors: Bowen
authors: School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, LE12 5RD.
authors: J A
authors: JA
authors: Leigh
authors: School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, LE12 5RD.
authors: T J
authors: TJ
authors: Coffey
authors: School of Veterinary Medicine and Science, Sutton Bonington Campus, University of Nottingham, LE12 5RD.
authors: R J
authors: RJ
authors: Flynn
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D002417:Cattle; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D006790:Host-Parasite Interactions / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D018688:Neospora / Q000276:immunology* / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000494:pharmacology; D014709:Vero Cells
chemical_list: C086500:DMBT1 protein, Bos taurus; D020381:Interleukin-17; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma