Unmethylated CpG motif-containing genomic DNA fragment ofBacillus calmette-guerin promotes macrophagefunctions through TLR9-mediated activation of NF-κB andMAPKs signaling pathways

摘要

The potency of synthetic CpG-oligo-deoxynucleotides (CpG-ODNs) adjuvantsin modulating the immune cell functions through the TLR pathway hasbeen tested and reported previously. However, the cellular signalinginvolved in the stimulation of macrophages by natural, CpGmotif-containing adjuvant and the effector functions modulated by suchstimulation has not been well studied. Here, we used and murine macrophageassay systems, and mouse model of stimulationto explore the signaling pathway and the effector functions mediatedby BC01. Results show that BC01 can induce the production of TNF-α andMCP-1 in macrophages by up-regulating the activation of NF-κB andMAPKs signaling pathway, and elevated the expression of MHC-II, CD40,CD80, and CD86. Upon stimulation with BC01, the peritoneal macrophagesisolated from TLR9 mice produced significantly lowlevels of pro-inflammatory cytokines, attenuated the activation ofNF-κB and MAPKs signaling pathways, and showed reduced phagocytosis.Following stimulation with BC01, theTLR9 mice produced significantly lower levels ofpro-inflammatory cytokines in the serum and lymph nodes showed reducedcell proliferation. These results indicate that BC01 is an efficientagonist of TLR9 that can significantly enhance the host-protectiveimmune functions of macrophages.