title: Reduced interferon-α production by dendritic cells in type 1 diabetes does not impair immunity to influenza virus.
abstract: The increased risk and persistence of infections in diabetic condition is probably associated with defects in the cellular immune responses. We have previously shown a decrease in the production of interferon (IFN)-α by dendritic cells (DCs) in diabetic subjects. The basal level of IFN-α in splenic plasmacytoid DCs (pDCs) is also lower in non-obese diabetic (NOD) mice compared to prediabetic mice. The objective of this study was to analyse the ability of diabetic mice to mobilize innate and CD8(+) T cell-mediated immune response to influenza A virus (IAV) with the live influenza A/Puerto Rico/8/1934 H1N1 (PR8) strain or with its immunodominant CD8(+) T cell epitopes. We found that following immunization with IAV, the level of IFN-α in diabetic mice was increased to the level in prediabetic mice. Immunization of NOD mice with the immunodominant IAV PR8 peptide induced clonal expansion of IFN-γ-producing CD8(+) T cells similar to the response observed in prediabetic mice. Thus, diabetic and prediabetic NOD mice have a similar capacity for IFN-α and IFN-γ production by pDCs and CD8(+) T cells, respectively. Therefore, the DC-related immune defect in diabetic NOD mice does not impair their capacity to develop an effective immune response to IAV. Our results suggest that reduced IFN-α production by diabetic human and mouse DCs is not an impediment to an effective immunity to IAV in type 1 diabetic subjects vaccinated with live attenuated influenza vaccine.
authors.affiliation: Centre for Human Immunology, Department of Microbiology and Immunology and Robarts Research Institute, University of Western Ontario, London, ON, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Kreuzer
authors.forename: E
authors.initials: E
authors.lastname: Nikoopour
authors.forename: B C Y
authors.initials: BC
authors.lastname: Au
authors.forename: O
authors.initials: O
authors.lastname: Krougly
authors.forename: E
authors.initials: E
authors.lastname: Lee-Chan
authors.forename: K L
authors.initials: KL
authors.lastname: Summers
authors.forename: S M M
authors.initials: SM
authors.lastname: Haeryfar
authors.forename: B
authors.initials: B
authors.lastname: Singh
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D016898:Interferon-alpha / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D016688:Mice, Inbred NOD; D009976:Orthomyxoviridae Infections / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D014764:Viral Proteins / Q000276:immunology / Q000494:pharmacology
chemical_list: D016898:Interferon-alpha; D010455:Peptides; D014764:Viral Proteins; D007371:Interferon-gamma
keywords: cytotoxic T cells; dendritic cells; diabetes; vaccination