Protection Against or Triggering of Type 1 Diabetes?
Protection Against or Triggering of Type 1 Diabetes?
The emergence of autoreactivity that ultimately destroys insulin-producing β-cells and causes Type 1 diabetes (T1D) is a result of genetic susceptibility and environmental factors, such as viral infections. The ability to induce strong cellular immune responses and to cause inflammation in the target organ makes viral infections prime candidates for the initiation of islet autoreactivity. Indeed, certain viruses have been linked to the occurrence of T1D based on epidemiological, serological and histological findings; and several rodent studies clearly demonstrate that viral infections can trigger autoimmunity. However, viruses have also been shown to efficiently prevent autoimmunity, which underlines the beneficial aspects of exposure to microbial agents as suggested by the hygiene hypothesis. Here, we will try to untangle some aspects of the complex interplay between viruses and the immune system and we will recapitulate by what rationale certain viruses have been associated with T1D.
The destruction of insulin-producing pancreatic β-cells by an autoreactive immune system is the hallmark of Type 1 diabetes (T1D) and the demise of pancreatic β-cell mass progressively impairs the body's blood glucose control. The necessity to closely monitor blood glucose levels and inject insulin accordingly is the inherent consequence for affected patients. Although insulin therapy has shown marked improvements over the last few decades, disease progresses in the vast majority of diabetic patients and long-standing dysglycemia results in macroangiopathic, microangiopathic or neuropathic complications. The incidence rates of T1D have been rising over the past few decades worldwide by an average of 3% per year and it has recently been predicted that T1D incidence may double in children under the age of 5 years by the year 2020, especially in developed countries.
While T1D is a genetic disorder and several genetic variations can undoubtedly be associated with disease occurrence, environmental factors that are largely unknown are thought to ultimately trigger diabetogenesis in susceptible individuals (reviewed in ). This concept evolved for several reasons. First, to date no genetic pattern has been described that leads to total disease penetration. Second, the concordance rate in monozygotic twins is well below 50%. Finally, disease occurs even in those individuals that carry protective genetic variations. Environmental triggers that turn genetic susceptibility into overt diabetes have drawn much attention, since a detailed knowledge of these factors may be key to preventing the disease in the future.
Even though several other factors may contribute to T1D pathogenesis, there is compelling evidence that viruses are major players in both disease initiation and in disease protection. In this article, we will summarize which viruses have been associated with T1D and recapitulate some aspects of the complex interplay between viruses and the immune system that result in the protection against, or triggering of, T1D.
Abstract and Introduction
Abstract
The emergence of autoreactivity that ultimately destroys insulin-producing β-cells and causes Type 1 diabetes (T1D) is a result of genetic susceptibility and environmental factors, such as viral infections. The ability to induce strong cellular immune responses and to cause inflammation in the target organ makes viral infections prime candidates for the initiation of islet autoreactivity. Indeed, certain viruses have been linked to the occurrence of T1D based on epidemiological, serological and histological findings; and several rodent studies clearly demonstrate that viral infections can trigger autoimmunity. However, viruses have also been shown to efficiently prevent autoimmunity, which underlines the beneficial aspects of exposure to microbial agents as suggested by the hygiene hypothesis. Here, we will try to untangle some aspects of the complex interplay between viruses and the immune system and we will recapitulate by what rationale certain viruses have been associated with T1D.
Introduction
The destruction of insulin-producing pancreatic β-cells by an autoreactive immune system is the hallmark of Type 1 diabetes (T1D) and the demise of pancreatic β-cell mass progressively impairs the body's blood glucose control. The necessity to closely monitor blood glucose levels and inject insulin accordingly is the inherent consequence for affected patients. Although insulin therapy has shown marked improvements over the last few decades, disease progresses in the vast majority of diabetic patients and long-standing dysglycemia results in macroangiopathic, microangiopathic or neuropathic complications. The incidence rates of T1D have been rising over the past few decades worldwide by an average of 3% per year and it has recently been predicted that T1D incidence may double in children under the age of 5 years by the year 2020, especially in developed countries.
While T1D is a genetic disorder and several genetic variations can undoubtedly be associated with disease occurrence, environmental factors that are largely unknown are thought to ultimately trigger diabetogenesis in susceptible individuals (reviewed in ). This concept evolved for several reasons. First, to date no genetic pattern has been described that leads to total disease penetration. Second, the concordance rate in monozygotic twins is well below 50%. Finally, disease occurs even in those individuals that carry protective genetic variations. Environmental triggers that turn genetic susceptibility into overt diabetes have drawn much attention, since a detailed knowledge of these factors may be key to preventing the disease in the future.
Even though several other factors may contribute to T1D pathogenesis, there is compelling evidence that viruses are major players in both disease initiation and in disease protection. In this article, we will summarize which viruses have been associated with T1D and recapitulate some aspects of the complex interplay between viruses and the immune system that result in the protection against, or triggering of, T1D.