Dysregulated TLR3-dependent signaling and innate immune activation in superoxide-deficient macrophages from nonobese diabetic mice

► Loss of superoxide decreases TLR3 and TRIF expression and TNF-α and IFN-α/β synthesis in poly(I:C)-stimulated NOD.Ncf1m1J macrophages. ► Defects in NF-κB signaling may account for dysregulated TLR3 expression. ► Exogenous superoxide can rescue TNF-α, but not IFN-α/β production; thus, type I interferon synthesis may be mediated in part by a NOX-independent mechanism. ► Compromised antiviral and innate immune responses in NOX-deficient NOD mice may partially explain resistance to type 1 diabetes.