Immunology in the clinic review series; focus on type 1 diabetes and viruses: the innate immune response to enteroviruses and its possible role in regulating type 1 diabetes

Abstract

Type 1 diabetes (T1D) is an autoimmune disease arising as a consequence of a misdirected T cell response to the pancreatic beta cell. In recent years, there has been a growing interest in the innate immune system as a regulator of disease development. Genome-wide association studies have identified diabetes-associated polymorphisms in genes encoding proteins with functions related to the innate immune response. Moreover, enteroviruses, known to activate a strong innate immune response, have been implicated in the disease pathogenesis. In this review, we discuss the innate immune response elicited by enteroviruses and how this response may regulate T1D development.

Fig. 1

An imbalanced innate immune response may have adverse consequences for the outcome of enterovirus infections and thereby contribute to Type 1 diabetes (T1D) development. During an acute viral infection, the innate immune system plays an important role by limiting early viral replication and spread, thereby allowing the host to mount an adaptive immune response. Although a strong innate immune response may be efficient in limiting viral dissemination and damage, it may also contribute to unwanted tissue damage. A weak response may favour viral replication and spread and thereby also tissue damage. Numerous gene loci associated with risk for T1D development contain gene candidates involved in the innate immune response. While it remains unclear how these different gene versions are involved in the disease process, some are likely to affect the response to an enterovirus infection.