Fig. 11

Schema of signaling pathway involved in HSP60-mediated NLRP3 inflammasome activation and subsequent IL-1β production. IL-1β induces its own production by the activated microglia in a HSP60-dependent manner. HSP60, after being upregulated by IL-1β, gets secreted outside and binds with TLR4 of the microglia to activate p38 MAPK [10]. Binding of HSP60 with TLR4 facilitates NF-κB phosphorylation, mitochondrial damage, and ROS generation and finally activates NLRP3 inflammasome leading to IL-1β production. JEV also augments HSP60 production and thus influences inflammasome complex to induce a consecutive expression of IL-1β and, in turn, induces an exaggerated immune response