title: Interactions between natural killer cells and dendritic cells favour T helper1-type responses to BCG in calves.
abstract: Vaccination of neonatal calves with BCG induces a significant level of protection from infection with Mycobacterium bovis, the causative agent of bovine tuberculosis. Since neonatal vaccination of humans with BCG induces activation of NK cells, and young calves have high circulating numbers of these cells, we hypothesised that NK cells are important in the protective response to BCG. Furthermore, since NK cells play a role in shaping adaptive immune responses through interactions with DCs, we investigated the interactions between NK cells and DCs in the context of BCG. DCs infected with BCG expressed significantly higher levels of MHC class II and the co-stimulatory molecules CD40 and CD80, alongside augmented production of the Th1 polarising cytokine IL-12, when compared with uninfected DCs. Following in vitro co-culture with BCG-infected DCs, NK cells increased their expression of the activatory molecule CD25, with preferential activation of the CD2- NK cell subset. NK cell effector function, as measured by production of IFN-γ, was also significantly enhanced following co-culture with BCG-infected DCs. This study provides novel evidence to demonstrate that NK cells phenotypically and functionally mature after interactions with DCs in the context of BCG. Furthermore, through the production of IFN-γ and IL-12 by NK cells and DCs respectively, this interaction may drive protective Th1-type immune responses to Mycobacteria.
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK. carly.hamilton@roslin.ed.ac.uk.
authors.forename: Carly A
authors.identifier: 0000-0002-2487-6838
authors.initials: CA
authors.lastname: Hamilton
authors.affiliation: Zoetis, Portage Street, Kalamazoo, MI, 49007, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Mahan
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.|Moredun Research Institute, Pentlands Science Park, Bush Loan, Midlothian, EH26 0PZ, Scotland, UK.
authors.forename: Gary
authors.initials: G
authors.lastname: Entrican
authors.affiliation: The Roslin Institute, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland, UK.
authors.forename: Jayne C
authors.initials: JC
authors.lastname: Hope
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology / Q000382:microbiology; D018122:B7-1 Antigen / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002417:Cattle; D003713:Dendritic Cells / Q000502:physiology*; D005455:Fluorescent Antibody Technique / Q000662:veterinary; D018664:Interleukin-12 / Q000378:metabolism; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007694:Killer Cells, Natural / Q000502:physiology*; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000502:physiology*; D014380:Tuberculosis, Bovine / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen; D001500:BCG Vaccine; D019013:CD40 Antigens; D053645:Interleukin-2 Receptor alpha Subunit; D018664:Interleukin-12