Toll-like receptor 3 (TLR3) and the development of type 1 diabetes mellitus

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic, progressive autoimmune disease characterized by metabolic decompensation often leading to dehydration and ketoacidosis. Viral agents seem to play an important role in triggering the autoimmune destruction that leads to the development of T1DM. Among several viral strains investigated so far, the enterovirus family has been consistently associated with the onset of T1DM in humans. One of the mediators of viral damage is the doublestranded RNA (dsRNA) generated during replication and transcription of viral RNA and DNA. The Toll-like receptor 3 (TLR3) gene codes for an endoplasmic receptor of the pattern-recognition receptors (PRRs) family that recognizes dsRNA, plays an important role in the innate immune response triggered by viral infection. Binding of dsRNA to the TLR3 triggers the release of proinflammatory cytokines, such as interferons, which exhibit potent antiviral action; thus, protecting uninfected cells and inducing apoptosis of infected ones. Therefore, the TLR3 gene is a good candidate for the development of T1DM. Within this context, the objective of the present review was to address the role of the TLR3 gene in the development of T1DM. Arch Endocrinol Metab. 2015;59(1):4-12

The role of the innate immune system in destruction of pancreatic beta cells in NOD mice and humans with type I diabetes

“…The expression of TLR3 has been observed in a number of human tissues including placenta, pancreas, lung, liver, heart, lymph nodes and brain [43]. TLR3 is usually expressed intracellularly in various human and mouse immune cells including T cells, macrophages, DCs, natural killer cells and γδ T cells [44, 45].…”

“…Thus, TLR3 could play a role in human T1D. To further examine this possibility, studies have shown an association of TLR3 and T1D in different populations from South Africa, UK, Finland and Brazil [43, 60-62]. Most of the data indicated a strong association of SNPs in the TLR3 pathway or polymorphisms of the TLR3 gene with T1D [43, 60-62].…”

“…To further examine this possibility, studies have shown an association of TLR3 and T1D in different populations from South Africa, UK, Finland and Brazil [43, 60-62]. Most of the data indicated a strong association of SNPs in the TLR3 pathway or polymorphisms of the TLR3 gene with T1D [43, 60-62]. However, recent studies in Polish and Norwegian patients with T1D and healthy controls did not find an association between TLR3 polymorphisms and the risk for autoimmune destruction of β cells [63, 64].…”

Diclofenac inhibits virulence of Proteus mirabilis isolated from diabetic foot ulcer

“…Inspite, the vast advances in controlling diabetes, complications usually happen. The most serious complications are those due to bacterial infections, particularly, in immunocompromised patients (Assmann et al, 2015). In this study, P. mirabilis was isolated from diabetic foot ulcer and its virulence behavior and resistance to common prescribed antibiotics were evaluated.…”

Dietary gluten and the development of celiac disease and type 1 diabetes

“…72 Similarly, the TLR3 and TLR4 genes, which play an important role in the innate immune response triggered by viral infection, are responsible for the development of both T1DM and CD. 42,73,74 …”