title: In vitro effects of the toll-like receptor agonists monophosphoryl lipid A and CpG-rich oligonucleotides on cytokine production by equine cells.
abstract: Insect bite hypersensitivity (IBH) is an equine allergic dermatitis to Culicoides spp. antigens. Attempts at using allergen-specific immunotherapy (AIT) as a treatment for IBH have so far proven unsuccessful. Toll-like receptor (TLR) agonists can promote a shift in the immune response from the allergy-promoting T helper cell 2 (Th2) response towards a Th1 and/or regulatory response. The aim of this study was to evaluate two immunomodulatory TLR agonists in vitro as potential vaccine adjuvants for a more efficacious AIT in IBH. Peripheral blood mononuclear cells (PBMCs) from healthy and IBH-affected horses were stimulated with the TLR-agonists monophosphoryl lipid A (MPLA) or CpG-rich oligodeoxynucleotides (CpG-ODN) in the presence or absence of Culicoides spp. allergens. Cytokine concentrations of interferon (IFN)-α, IFN-γ, interleukin (IL)-4, IL-10 and IL-17 were quantified in the supernatants of stimulated PBMCs. MPLA induced IL-10 secretion in all horses, regardless of presence and nature of antigens, while suppressing antigen-induced production of IFN-γ, IL-4 and IL-17. CpG-ODN significantly increased IFN-α, IFN-γ and IL-4 production, but had little effect on IL-10 production. In conclusion, MPLA promotes a regulatory immune response and is therefore a promising adjuvant candidate for allergy vaccines in horses. While C-class CpG-ODN is an unsuitable adjuvant for AIT, it induces IFN-γ and IFN-α, and thus may be a useful adjuvant in combination with vaccines for equine infectious or neoplastic diseases.
authors.affiliation: Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Länggass-Strasse 124, Bern CH-3001, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Ziegler
authors.affiliation: Swiss Institute of Equine Medicine, University of Bern and Agroscope, Länggass-Strasse 124, Bern CH-3001, Switzerland.
authors.forename: V
authors.initials: V
authors.lastname: Gerber
authors.affiliation: Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Länggass-Strasse 124, Bern CH-3001, Switzerland. Electronic address: eliane.marti@vetsuisse.unibe.ch.
authors.forename: E
authors.initials: E
authors.lastname: Marti
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism*; D006736:Horses / Q000378:metabolism*; D007155:Immunologic Factors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: C408982:CPG-oligonucleotide; D016207:Cytokines; D007155:Immunologic Factors; D008050:Lipid A; D009838:Oligodeoxyribonucleotides; D051193:Toll-Like Receptors; C048436:monophosphoryl lipid A
keywords: Adjuvant; CpG-rich oligonucleotides; Equine; Hypersensitivity; Monophosphoryl lipid A