Activation of NLRP3 inflammasome in DV-infected GM-Mϕ. GM-Mϕ is infected with DV directly (A), or after LPS priming (B). DV binding to CLEC5A recruits DAP12, which is phosphorylated by Src, and then activates Syk. Activated Syk induces the transcription of IL-1β, IL-18, and NLRP3 to activate inflammasome and caspase-1, leading to cell death (pyroptosis) and cleavage of pro-IL-1β and pro-IL-18. Secondary signaling, potassium efflux, and lysosome cathepsin B are also involved in NLRP3 inflammasome activation and the release of IL-1β and-IL-18 from DV–infected GM-Mϕ. LPS priming further enhances the transcription of IL-1β (significantly), IL-18 (slightly), and NLRP3 (slightly), and further increases the secretion of IL-1β. DV, dengue virus; NLRP, NLR family PYD-containing protein; LPS, lipopolysaccharides; IL-1β, interleukin -1beta.