Immunology in the clinic review series: focus on type 1 diabetes and viruses: the role of viruses in type 1 diabetes: a difficult dilemma

Abstract

SummaryConvincing evidence now indicates that viruses are associated with type 1 diabetes (T1D) development and progression. Human enteroviruses (HEV) have emerged as prime suspects, based on detection frequencies around clinical onset in patients and their ability to rapidly hyperglycaemia trigger in the non-obese diabetic (NOD) mouse. Whether or not HEV can truly cause islet autoimmunity or, rather, act by accelerating ongoing insulitis remains a matter of debate. In view of the disease's globally rising incidence it is hypothesized that improved hygiene standards may reduce the immune system's ability to appropriately respond to viral infections. Arguments in favour of and against viral infections as major aetiological factors in T1D will be discussed in conjunction with potential pathological scenarios. More profound insights into the intricate relationship between viruses and their autoimmunity-prone host may lead ultimately to opportunities for early intervention through immune modulation or vaccination.

Environmental risk factors for type 1 diabetes

“…Bacterial infections are rarely discussed, although bacteria as a cause of pancreatic lesions cannot be excluded. Several viruses have been implicated, with enteroviruses having the strongest evidence from studies in animal models 20 and in human beings. 21 These viruses have a tropism to human pancreatic islets in vivo and in vitro, 19, 22 and have been detected in the pancreas of patients recently diagnosed with type 1 diabetes.…”

Genetic Risk Factors for Pancreatic Disorders

“…Located in the back of the abdomen, the pancreas is well protected from mechanical injury and from direct interactions with the environment, toxins, and infectious agents. As a result, pancreatic diseases are relatively rare, with the exception of type 1 diabetes mellitus (T1DM), which results from autoimmune-associated destruction of the pancreatic islet β cells 10 . AP and CP are the most common disorders of the exocrine pancreas, and in contrast to T1DM, the mechanism of injury or destruction is generally not autoimmune-mediated.…”

The pancreatic β cell and type 1 diabetes: innocent bystander or active participant?

“…Viral infections remain one of the most likely candidates, although the evidence for viral infection and, more importantly, the specific viral types responsible for T1DM are still subject to much debate [49]. Detection of viral dsRNAs by RIG-I and IFIH1 leads to activation of the innate immune system and of transcription factors, such as IFN-regulatory factors (IRFs) and nuclear factor κB (NF-κB), ultimately leading to the production of type 1 IFN and other proinflammatory cytokines [50].…”