title: Differential expression of Toll-like receptors and inflammatory cytokines in ovine interdigital dermatitis and footrot.
abstract: Footrot is a common inflammatory bacterial disease affecting the health and welfare of sheep worldwide. The pathogenesis of footrot is complex and multifactorial. The primary causal pathogen is the anaerobic bacterium Dichelobacter nodosus, with Fusobacterium necrophorum also shown to play a key role in disease. Since immune-mediated pathology is implicated, the aim of this research was to investigate the role of the host response in interdigital dermatitis (ID) and footrot. We compared the expression of Toll-like receptors (TLRs) and pro-inflammatory cytokines and the histological appearance of clinically normal in comparison to ID and footrot affected tissues. Severe ID and footrot were characterised by significantly increased transcript levels of pro-inflammatory cytokines TNFα and IL1β and the pattern recognition receptors TLR2 and TLR4 in the interdigital skin. This was reflected in the histopathological appearance, with ID and footrot presenting progressive chronic-active pododermatitis with a mixed lymphocytic and neutrophilic infiltration, gradually increasing from a mild form in clinically normal feet, to moderate in ID and to a focally severe form with frequent areas of purulence in footrot. Stimulation with F. necrophorum and/or D. nodosus extracts demonstrated that dermal fibroblasts, the resident cell type of the dermis, also contribute to the inflammatory response to footrot bacteria by increased expression of TNFα, IL1β and TLR2. Overall, ID and footrot lead to a local inflammatory response given that expression levels of TLRs and IL1β were dependent on the disease state of the foot not the animal.
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Loughborough LE12 5RD, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Davenport
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Loughborough LE12 5RD, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Heawood
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Loughborough LE12 5RD, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Sessford
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Loughborough LE12 5RD, UK.
authors.forename: Melissa
authors.initials: M
authors.lastname: Baker
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Loughborough LE12 5RD, UK.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Baiker
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
authors.forename: Barbara
authors.initials: B
authors.lastname: Blacklaws
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Loughborough LE12 5RD, UK.
authors.forename: Jasmeet
authors.initials: J
authors.lastname: Kaler
authors.affiliation: School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Green
authors.affiliation: School of Veterinary Medicine and Science, University of Nottingham, Loughborough LE12 5RD, UK. Electronic address: sabine.totemeyer@nottingham.ac.uk.
authors.forename: Sabine
authors.initials: S
authors.lastname: Tötemeyer
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003872:Dermatitis / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D005534:Foot Diseases / Q000276:immunology / Q000378:metabolism / Q000662:veterinary*; D005786:Gene Expression Regulation / Q000276:immunology*; D008214:Lymphocytes; D009504:Neutrophils; D012756:Sheep; D012757:Sheep Diseases / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors
keywords: Cytokines; Footrot; Histopathology; Inflammation; Sheep; Toll-like receptor