Impaired Innate Immunity in Pediatric Patients Type 1 Diabetes—Focus on Toll-like Receptors Expression

Abstract

Type 1 diabetes (DM1) is classified as an autoimmune disease. An uncontrolled response of B and T lymphocytes to the body’s own tissues develops in the absence of immune tolerance. The main aim of the study was to evaluate the effect of the duration of type 1 diabetes in children on the expression of TLR receptors and the relationship with the parameters of glycemic control in patients. As a result, we showed significant differences in the level of TLR2, TLR4 and TLR9 expression in patients with DM1 in the early stage of the disease and treated chronically compared to the healthy group. Additionally, in this study, we found that the numbers of CD19+ B cells, CD3+ CD4+, CD3+ CD8+ T cells and NK cells are different for newly diagnosed DM1 individuals, patients receiving chronic treatment and for healthy controls, indicating an important role of these cells in killing pancreatic beta cells. Moreover, higher levels of IL-10 in patients with newly diagnosed DM1 have also been found, confirming the reports found in the literature.

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“…Here, focusing on adults with longstanding T1D, we show that they have a more active immunological profile as compared to age-matched healthy controls. Consistent with previous studies in children with established diabetes showing an increase of circulating neutrophils and a decrease of NK cells (7,24), we also observed enhanced neutrophil and diminished NK proportions in adults affected for more than 20-years with diabetes. However, in contrast to the lower circulating monocyte proportions found in paediatric patients diagnosed for less than 2-years with diabetes (27), we observed enhanced percentages and absolute numbers of monocytes in adults with longstanding T1D as compared to healthy controls.…”

“…We and others have shown that blood immune cell profiling approaches are a powerful tool for detailed characterization of immune cell subsets in peripheral blood of healthy individuals and patients (18,(22)(23)(24). The association of peripheral immune cell changes and disease progression of type 1 diabetes has been shown in several studies, especially in newly diagnosed diabetes patients (6,7,(23)(24)(25)(26). Here, focusing on adults with longstanding T1D, we show that they have a more active immunological profile as compared to age-matched healthy controls.…”

“…Next to the involvement of immune cells in T1D pathogenesis and disease progression, immune suppressive regulatory T cells (Treg) are crucial in the prevention/delay of disease progression. Lack of Treg accelerated T1D disease onset in a murine model (7). Treg of T1D patients showed an impaired capacity to control effector T cells, and the patients CD4+ cells were thought to be relatively resistant to regulation by Treg (8,9).…”

Lower percentages of natural killer cells in children with type 1 diabetes and their siblings

“…NK cell activation occurs as a result of NKp46 fusion with unknown ligands on pancreatic b cells. The authors showed that the lack of NKp46 receptor, or blocking its activity, inhibits the development of T1DM [28,55]. Aboelnazar et al also assessed the expression of NK and NKp46+ cells.…”

Precision Vaccinology Approaches for the Development of Adjuvanted Vaccines Targeted to Distinct Vulnerable Populations

“…Thus, with more advanced targeting screening tools for these endosomal targets, the arsenal of precision adjuvants available to vaccinate this vulnerable population can substantially advance. This framework can be more broadly applied to various vulnerable populations as we characterize population-specific immunity [ 50 , 51 , 52 ].…”