Protection against or triggering of Type 1 diabetes? Different roles for viral infections

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.

Figure 1. Schematic model of how viral infections with pancreatotropic viruses could have opposing outcomes depending on various factors

Pre-existing islet inflammation at the time of infection with a rapidly replicating virus, in the absence of protective immunity, could increase the chances of promoting or accelerating Type 1 diabetes onset through mechanisms such as bystander activation, molecular mimicry or antigenic spreading. By contrast, viral infection in the absence of insulitis is more likely to result in protection from Type 1 diabetes through upregulation of immunoregulatory mechanisms and acquisition of protective immunity that prevents infection at later time points when host-driven insulitis could be present.