Understanding the increased risk of infections in diabetes: innate and adaptive immune responses in type 1 diabetes

Aims: Patients with diabetes have a higher incidence of infections with Candida albicans, Staphylococcus aureus and Mycobacterium tuberculosis, yet factors contributing to this increased risk are largely unknown. We hypothesize that altered innate and adaptive immune responses during diabetes contribute to an increased susceptibility to infections. Materials and methods: We studied cytokine responses to ex vivo pathogenic stimulations in a cohort with type 1 diabetes (n = 243) and non-diabetic healthy control subjects (n = 56) using isolated peripheral blood mononuclear cells (PBMCs). Clinical phenotypical data including BMI, duration of diabetes, and HbA(1c) levels were collected and related to the cytokine production capacity. Results: Adjusted for age, sex and BMI, the presence of diabetes was associated with significantly lower IL-1 beta, IL-6, TNF-alpha, and IL-17 production upon ex vivo stimulation of PBMCs with C. albicans and S. aureus (all, p < 0.05). In response to stimulation with M. tuberculosis only IL-17 (p < 0.001) was lower in patients with diabetes. Patients with the shortest diabetes duration had a significant lower IL-1 beta, IL-6 and TNF-alpha production (all, p < 0.01) after M. tuberculosis stimulation. Older patients had a significant lower IFN-gamma (p < 0.05) production after stimulation with all three pathogens. HbA(1c) levels and BMI had no significant impact on cytokine production. Conclusions: PBMCs of patients with type 1 diabetes demonstrate significantly lower cytokine production in response to stimulation with several pathogens, which likely explain, at least in part, the increased susceptibility for these infections. (C) 2021 Published by Elsevier Inc.