Fig. 3

Schematic of representative bacterial-origin immunostimulants signaling pathway. (A) LPS and MPL interact with TLR4, recruiting its downstream adaptors. LPS induced both the MyD88-dependent and MyD88-independent signaling pathways, responsible for proinflammatory cytokine expression and Type I interferons, respectively. MPL activated the MyD88-independent signaling mediating the induction of Type I interferons. (B) The signaling cascade induction by flagellin can be through MyD88-dependent and MyD88-independent pathways. Flagellin activates the dimerization of TLR5 and then recruited MyD88 binding to the cytoplasmic portion of TLR5. The interaction leads to the activation of NF-κB signaling, inducing many downstream inflammatory-related genes expression. Meanwhile, TLR5 can form heteromeric complexes with TLR4 induced with flagellin, which lead to the activation of MyD88-independent signaling and production of NO. (C) Cytoplasmic flagellin activates caspase-1 and secretion of IL-1β via NLRC4/NAIP5-dependent inflammasome pathway. (D) CpG-ODN interacts with TLR9 in the endosome and recruits MyD88 and the downstream molecules, which activates either NF-κB or IRF7 according to the type of endosomes. The activation of NF-κB is responsible for the production of pro-inflammatory cytokines, like IL-1, IL-6, IL-12, and TNF-α, while the activation of IRF-7 is responsible for the expression of type I interferons. LPS, lipopolysaccharide; MPL, monophosphoryl lipid A; TLR, Toll-like receptors; MyD88, myeloid differentiation 88; NO, nitric oxide; IL, interleukin; NLRC4, Nod-like receptor protein 4; NAIP5, Nucleotide-binding domain leucine-rich repeat family, apoptosis inhibitory protein 5; CpG-ODN, CpG Oligodeoxynucleotides; IRF7, Interferon regulatory factor 7; TNF, tumor necrosis factor