It is thus tempting to speculate that the noted difference is driven by the very inefficient entry, and infection of the immature DENV in PBMCs vs in pDCs enriched population, as consequence, the differential engagement of intracellular pattern recognition receptors sensing viral RNA and replication intermediates e.g., TLR3, TLR7, TLR8, RIG-I and MDA5 [12–14]. This evidence concerns the gene IFIH1 and infection.