Enterovirus Infection of Human β-Cells Activates Dendritic Cells and Triggers Innate Antiviral Responses: Are Enteroviruses Convicted Now?

摘要

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 cox-sackievirus 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: i) 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.