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

Clin Exp Immunol. 2015 Feb;179(2):245-55. doi: 10.1111/cei.12462.

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.

Keywords: cytotoxic T cells; dendritic cells; diabetes; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / pathology
  • Humans
  • Immunity, Cellular*
  • Immunization
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Interferon-alpha / immunology*
  • Interferon-gamma / pharmacology
  • Mice
  • Mice, Inbred NOD
  • Orthomyxoviridae Infections / immunology
  • Peptides / immunology
  • Peptides / pharmacology
  • Viral Proteins / immunology
  • Viral Proteins / pharmacology

Substances

  • Interferon-alpha
  • Peptides
  • Viral Proteins
  • Interferon-gamma