Reduced interferon‐α production by dendritic cells in type 1 diabetes does not impair immunity to influenza virus

• Published in: Clinical and experimental immunology Vol. 179; no. 2; pp. 245 - 255
• Main Authors: Kreuzer, D., Nikoopour, E., Au, B. C. Y., Krougly, O., Lee‐Chan, E., Summers, K. L., Haeryfar, S. M. M., Singh, B.
• Format: Journal Article
• Language: English
• Published: England BlackWell Publishing Ltd 01.02.2015
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; cytotoxic T cells; dendritic cells; Dendritic Cells - immunology; Dendritic Cells - pathology; diabetes; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - pathology; Humans; Immunity, Cellular; Immunization; Influenza A virus; Influenza A Virus, H1N1 Subtype - immunology; Interferon-alpha - immunology; Interferon-gamma - pharmacology; Mice; Mice, Inbred NOD; Original; Orthomyxoviridae Infections - immunology; Peptides - immunology; Peptides - pharmacology; vaccination; Viral Proteins - immunology; Viral Proteins - pharmacology; ASW, Caribbean Sea, Greater Antilles, Puerto Rico; dendritic cells; cytotoxic T cells; diabetes; vaccination
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12462

Summary 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.