Theoretical model for IL-10 production and its pathogenic role during DENV infection. IL-10 is produced in T cells (TH2 and Treg) through an unknown mechanism and in Fcγ receptor-bearing cells directly through viral receptors and indirectly through an ADE-facilitated manner. The extrinsic ADE pathway occurs through Fcγ receptor-facilitated virus contact and entry following viral receptor-mediated endocytosis. An alternative intrinsic ADE pathway may trigger Fcγ receptor-mediated signaling to activate Syk/PKC/ERK-regulated IL-10 expression. However, the molecular mechanisms for IL-10 production remain unclear. Crosstalk between PKC/PKA/PKB-regulated GSK-3 for the transcriptional regulation of IL-10 and the involvement of genetic factors are also summarized. IL-10-regulated SOCS3 expression may benefit DENV replication by facilitating IFN resistance.