Key points are not available for this paper at this time.
Introduction & Objective: Viruses, particularly members of the picornavirus family, are correlated with the onset of T1D. For this reason, viral infection has been identified as an environmental trigger for T1D onset, specifically due to its ability to stimulate the production and release of pro-inflammatory cytokines into the islet. The purpose of this study is to define physiological functions of cytokine signaling in β-cells that may contribute to reduced virus-mediated damage and destruction of β-cells. Methods: C57BL/6J and DBA/2J mice were infected with encephalomyocarditis virus (EMCV), a highly inflammatory picornavirus that causes dysglycemia in genetically susceptible mouse strains. Pancreas and serum were collected from the animals throughout the course of infection. Insulitis and β-cell morphology were evaluated by H&E and immunofluorescence and serum cytokine concentrations were analyzed by LEGENDplex anti-virus response assay. Furthermore, isolated mouse islets were treated with cytokines and gene responses and EMCV viral replication were measured by qRT-PCR. Results: We show that C57BL/6J mice are resistant to EMCV infection and maintain islet architecture and glycemic control, despite immune cell infiltration. In contrast, EMCV infection of genetically susceptible DBA/2J mice results in destruction of β-cells, deterioration of islet morphology, and loss of glycemic control. Transiently elevated serum cytokines in C57BL/6J mice suggest successful restriction of EMCV replication whereas sustained elevation of these cytokines in DBA/2J mice suggests a failure of these mice to mount an effective antiviral response. Additionally, islets treated with IL-1β ex-vivo upregulate several antiviral genes and treatment of isolated islets with IL-1β prior to infection attenuates EMCV mRNA accumulation. Conclusion: These studies suggest IL-1β signaling in β-cells during viral infection functions to activate protective antiviral defense mechanisms designed to limit β-cell damage. Disclosure J. Bartosiak: None. J.A. Corbett: None. Funding AI2212769
BARTOSIAK et al. (Fri,) studied this question.