Enterovirus infection and type 1 diabetes: unraveling the crime scene

Enteroviruses (EV) have been historically associated to type 1 diabetes. Definitive proof for their implication in disease development is lacking, but growing evidence suggests that they could be involved in beta cell destruction either directly by killing beta cells or indirectly by creating an exacerbated inflammatory response in the islets, capable of attracting autoreactive T cells to the ‘scene of the crime’. Increasing evidence in the field shows that a ‘viral signature’ exists in type 1 diabetes and involves interferon responses that could be sustained during prolonged periods. These include the up‐regulation of markers such as protein kinase R (PKR), melanoma differenti ation‐associated protein 5 (MDA5), retinoic acid inducible gene I (RIG‐I), myxovirus resistance protein (MxA) and human leukocyte antigen‐I (HLA‐I) and the release of chemokines able to attract immune cells to the islets leading to insulitis. In this scenario, the hyperexpression of HLA‐I molecules would promote antigen presentation to autoreactive T cells, favoring beta cell recognition and, ultimately, destruction. In this review, an overview of the standing evidence that implicates EVs in beta cell ‘murder’ is provided, the time‐line of events from EV entry in the cell to be ta cell death is investigated and possible accomplices that might be involved in beta cell demise are highlighted. SummaryEnteroviruses (EV) have been historically associated to type 1 diabetes. Definit...

Source: Clinical and Experimental Immunology - November 13, 2018 Category: Allergy & Immunology Authors: T. Rodriguez ‐Calvo Tags: Review Article Source Type: research