title: Badger macrophages fail to produce nitric oxide, a key anti-mycobacterial effector molecule.
abstract: The European badger is recognised as a wildlife reservoir for bovine tuberculosis (bTB); the control of which is complex, costly and controversial. Despite the importance of badgers in bTB and the well-documented role for macrophages as anti-mycobacterial effector cells, badger macrophage (bdMφ) responses remain uncharacterised. Here, we demonstrate that bdMφ fail to produce nitric oxide (NO) or upregulate inducible nitric oxide synthase (iNOS) mRNA following Toll-like receptor (TLR) agonist treatment. BdMφ also failed to make NO after stimulation with recombinant badger interferon gamma (bdIFNγ) or a combination of bdIFNγ and lipopolysaccharide. Exposure of bdMφ to TLR agonists and/or bdIFNγ resulted in upregulated cytokine (IL1β, IL6, IL12 and TNFα) mRNA levels indicating that these critical pathways were otherwise intact. Although stimulation with most TLR agonists resulted in strong cytokine mRNA responses, weaker responses were evident after exposure to TLR9 agonists, potentially due to very low expression of TLR9 in bdMφ. Both NO and TLR9 are important elements of innate immunity to mycobacteria, and these features of bdMφ biology would impair their capacity to resist bTB infection. These findings have significant implications for the development of bTB management strategies, and support the use of vaccination to reduce bTB infection in badgers.
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, United Kingdom.|Wildlife Conservation Research Unit Department of Zoology, University of Oxford, The Recanati-Kaplan Centre, Tubney House, Abingdon Road, Tubney, Abingdon OX13 5QL, United Kingdom.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Bilham
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, United Kingdom.
authors.forename: Amy C
authors.initials: AC
authors.lastname: Boyd
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, United Kingdom.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Preston
authors.affiliation: Wildlife Conservation Research Unit Department of Zoology, University of Oxford, The Recanati-Kaplan Centre, Tubney House, Abingdon Road, Tubney, Abingdon OX13 5QL, United Kingdom.
authors.forename: Christina D
authors.initials: CD
authors.lastname: Buesching
authors.affiliation: Wildlife Conservation Research Unit Department of Zoology, University of Oxford, The Recanati-Kaplan Centre, Tubney House, Abingdon Road, Tubney, Abingdon OX13 5QL, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Newman
authors.affiliation: Wildlife Conservation Research Unit Department of Zoology, University of Oxford, The Recanati-Kaplan Centre, Tubney House, Abingdon Road, Tubney, Abingdon OX13 5QL, United Kingdom.
authors.forename: David W
authors.initials: DW
authors.lastname: Macdonald
authors.affiliation: Department of Zoology, University of Oxford, South Parks Road, OX1 3PS, United Kingdom.
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Smith
mesh_terms: D000818:Animals; D002417:Cattle; D007093:Imidazoles / Q000494:pharmacology; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D045969:Mustelidae / Q000276:immunology / Q000378:metabolism*; D009161:Mycobacterium / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000145:classification / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014380:Tuberculosis, Bovine / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007093:Imidazoles; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C402365:resiquimod