Enterovirus Infection of Human β-Cells Activates Dendritic Cells and Triggers Innate Antiviral Responses: Are Enteroviruses Convicted Now?
- From the Clinic of the Goethe University Frankfurt am Main, Pharmazentrum Frankfurt/ZAFES, Frankfurt am Main, Germany.
- Corresponding author: Urs Christen, .
Despite a large number of epidemiologic associations, clinical studies, and animal models, a direct involvement of pathogens in the etiology of human type 1 diabetes is still a matter of critical debate. Human enteroviruses (HEV), such as coxsackievirus B (CVB) and echoviruses (EV), have been associated with type 1 diabetes since the late 1960s (1) and have been found in pancreatic isolates of type 1 diabetic patients (2–4) (rev. in 5). However, there are several difficulties hampering the conviction of HEV as inducers of type 1 diabetes: 1) pancreatic biopsies are not done on a regular basis in type 1 diabetic patients; 2) HEV infections are frequently found in nondiabetic individuals and often remain asymptomatic; 3) the clinical manifestation of type 1 diabetes may occur years to decades after infection (virus infection as a “hit-and-run” event); 4) type 1 diabetic patients as well as healthy individuals undergo multiple virus infections throughout their lifetime, some of which might even protect them from rather than induce autoimmune disease; and 5) genetic predispositions might cover possible environmental (i.e., virus) factors.
In this issue of Diabetes, Schulte et al. (6) address the mechanism by which HEV infection of human islets might influence type 1 diabetes onset and/or progression. They found that monocyte-derived dendritic cells (DCs) efficiently phagocytosed CVB3-infected human and porcine islets. Phagocytosis of CVB3-infected islets induced the …