Fig. 2

The design strategies for immunostimulants. Various types of immunostimulants activate different PRRs, leading to the secretion of various cytokines and inducing diverse adaptive immune responses. Immunostimulants activate TLRs, cGAS-STING, CLRs, other PRRs, or directly release cytokines to induce and modulate adaptive immune responses. Binding to TLRs heterodimers initiates MyD88 pathway and activated NF-κB and ERK1/2 to enhance pro-inflammatory cytokines. The mtDNA and dsDNA initiates the conversion of cGAS into cGAMP and consequently activates STING to release TBK to activates IRF 3 and IKKi to activates NF-κB. Finally, IRF 3 induces type 1 interferons, cross presentation and CTL and NF-κB induces pro-inflammatory cytokines and activate Th1 cells. Targeting to most CLRs activated NF-κB to enhance pro-inflammatory cytokines. Notably, targeting to CD205 and CD206 can enhance endocytosis and antigen presentation. Common immunostimulants targeting to NLRs (NOD 1 and NOD 2) activated NF-κB ultimately produces a predominantly Th2-type of immune response. Alternatively, immunostimulants targeting to MDA5 and RIG-I activate IRF 3 and IRF 7 respectively. At length, IRF 3 and IRF 7 induce type 1 interferons, cross presentation, CTL and activate Th1 cells