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.

Innate immune stimulation of whole blood reveals IFN-1 hyper-responsiveness in type 1 diabetes

“…This chronic IFN exposure over time may suppress the tonic, unstimulated response, but prime a stronger acute response, possibly via epigenetic changes [57]. This could explain why unstimulated ISG expression is high in individuals at risk for type 1 diabetes [19,26] and lower in established type 1 diabetes [58]. However, with strong acute stimulation, increased ISG expression is observed even after disease onset [59].…”

Nonobese Diabetic (NOD) Mice Lack a Protective B-Cell Response against the “Nonlethal”Plasmodium yoelii17XNL Malaria Protozoan

“…In addition, we have reported that immunization of prediabetic NOD mice with a preparation of UV-inactivated influenza virus PR8/A/34 induced a robust titer of neutralizing anti-viral antibodies [35]. Recently, it has been shown that the influenza virus infection does not impair the antiviral immune response in NOD mice [36]. Also, human studies showed no significant difference in the titers of anti-influenza viral antibodies between nonvaccinated, genetically predisposed children to T1D and control children [37].…”

Dissecting the interaction between COVID‐19 and diabetes mellitus

“…The humoral system, which mediates immediate defense responses by polymorphs, macrophages and dendritic antigen presenting cells to pathogens, is attenuated in diabetes mellitus 17 . Defects in adaptive immunity are associated with impaired type 1 interferon production 18 . Furthermore, increased generation of advanced glycation end-products could also inhibit the generation of interferon gamma by T lymphocytes 19 .…”