Abstract
BackgroundCpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-β in the immunomodulatory effects of CpG-ODN is not known.ObjectiveHere, we aimed to elucidate the role of IFN-β in the anti-allergic effect of CpG motifs.MethodsWe assessed the immune response in OVA-primed/OVA-challenged IFN-β knockout (-/-) mice compared to wild type (WT) control, after intranasal and systemic treatment with synthetic CpG motifs.ResultsVaccination with CpG-ODN reduced the number of cells in airways of OVA-sensitized WT but not IFN-β-/- mice. Although airway eosinophilia was reduced in both treated groups, they were significantly higher in IFN-β-/- mice. Other inflammatory cells, such as lymphocytes and macrophages were enhanced in airways by CpG treatment in IFN-β-/- mice. The ratio of IFN-γ/IL-4 cytokines in airways was significantly skewed to a Th1 response in WT compared to IFN-β-/- group. In contrast, IL-4 and IgE were reduced with no differences between groups. Ag-specific T-cell proliferation, Th1-cytokines such as IFN-γ, IL-2 and also IL-12 were significantly lower in IFN-β-/- mice. Surprisingly, we discovered that intranasal treatment of mice with CpG-ODN results in mild synovitis particularly in IFN-β-/- mice.ConclusionOur results indicate that induction of Th1 response by therapy with CpG-ODN is only slightly and partially dependent on IFN-β, while IFN-β is not an absolute requirement for suppression of airway eosinophilia and IgE. Furthermore, our finding of mild synovitis is a warning for possible negative effects of CpG-ODN vaccination.
Highlights
Allergic diseases are characterized by elevated serum IgE, an inflammatory reaction with increased number of eosinophils, mast cells and an adaptative immune responses orchestrated by Th2-like CD4+ memory T cells secreting an array of cytokines such as IL-4, IL-5 and IL-13
Our results indicate that induction of Th1 response by therapy with cytosine-guanine motifs (CpG)-ODN is only slightly and partially dependent on IFN-β, while IFN-β is not an absolute requirement for suppression of airway eosinophilia and IgE
Our results indicate that induction of Th1 response by therapy with CpG oligodeoxynucleotides (CpG-ODN) is partially dependent on IFN-β, while IFN-β is not an absolute requirement for suppression of eosinophilia and IgE
Summary
Allergic diseases are characterized by elevated serum IgE, an inflammatory reaction with increased number of eosinophils, mast cells and an adaptative immune responses orchestrated by Th2-like CD4+ memory T cells secreting an array of cytokines such as IL-4, IL-5 and IL-13. There are major efforts focused on a therapeutic treatment which will decrease the Th2 profile and/or re-direct the immune response from a Th2, IgE-mediated allergic hypersensitivity reaction towards the more favorable Th1 response. Difficulties with precise dosing and toxicity associated with the direct administration of these cytokines may preclude their therapeutic application. CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-β in the immunomodulatory effects of CpG-ODN is not known
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