title: Innate immune responses of airway epithelial cells to infection with equine herpesvirus-1.
abstract: Equine herpesvirus-1 (EHV-1) is the cause of respiratory disease, abortion and myelitis in horses worldwide. Protection following infection or vaccination is typically incomplete and this lack of protective immunity is thought to be due to the immunomodulatory properties of EHV-1. EHV-1 immune modulation is likely initiated early in the infection cycle at the respiratory epithelium, but to date, immunity to EHV-1 at the epithelial cell barrier remains poorly characterized. Thus, the purpose of this study was to use a recently established primary equine respiratory epithelial cell culture (EREC) system to characterize innate immunity to EHV-1. Differentiated ERECs were inoculated with a neuropathogenic strain of EHV-1 and cytokine responses were determined using quantitative real-time polymerase chain reaction and ELISA. Major histocompatibility complex (MHC)-I and MHC-II as well as toll-like receptor (TLR)3 and TLR9 protein expression were examined using fluorescence activated cell-sorting analysis and chemotaxis of neutrophils and monocytes were evaluated using chemotaxis assays. Infection with EHV-1 resulted in increased expression of TLR3 and 9 as well as inflammatory cytokines (IL-1, TNF-alpha, IFN-alpha, and IL-6) and chemokines (IL-8, MCP-1). In contrast, EHV-1 infection caused marked decreases of MHC-I and MHC-II expression as well as a reduction in IFN-gamma production. In summary, these results provide an initial characterization of the early immune response to EHV-1 at the epithelial cell barrier and show that, while EHV-1 maintains induction of an inflammatory response, it causes an attenuation of IFN-gamma responses and down-modulates expression of MHC-I and MHC-II, which are important molecules for antigen presentation.
authors.affiliation: Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Veterinary Medical Center, Room A13, 784 Wilson Road, East Lansing, MI 48824, USA. Electronic address: husseygi@msu.edu.
authors.forename: Gisela
authors.initials: G
authors.lastname: Soboll Hussey
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Road, Fort Collins, CO 80523, USA.
authors.forename: Laura V
authors.initials: LV
authors.lastname: Ashton
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Road, Fort Collins, CO 80523, USA.
authors.forename: Ayshea M
authors.initials: AM
authors.lastname: Quintana
authors.affiliation: North Carolina State University, 1060 William Moore Drive, Raleigh, NC 276074, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Lunn
authors.affiliation: Faculty of Veterinary Medicine, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Lutz S
authors.initials: LS
authors.lastname: Goehring
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Road, Fort Collins, CO 80523, USA.
authors.forename: Kristina
authors.initials: K
authors.lastname: Annis
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 300 W. Drake Road, Fort Collins, CO 80523, USA.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Landolt
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D005786:Gene Expression Regulation / Q000276:immunology; D006566:Herpesviridae Infections / Q000276:immunology / Q000662:veterinary*; D004861:Herpesvirus 1, Equid / Q000276:immunology*; D006734:Horse Diseases / Q000276:immunology*; D006736:Horses; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000821:virology*; D053586:Virus Internalization
chemical_list: D018925:Chemokines; D016207:Cytokines
keywords: EHV-1; Epithelium; Equine; Innate immunity