ADP-heptose is a pathogen-associated molecular pattern of Shigella flexneri infection

摘要: During an infection, the detection of pathogens is mediated through interactions between pathogen-associated molecular patterns (PAMPs) and pathogen recognition receptors. β-Heptose 1,7-bisphosphate (βHBP), a metabolite lipopolysaccharide (LPS) biosynthesis pathway, was recently identified as PAMP gram-negative bacteria. It reported that βHBP sensing leads within minutes to oligomerization protein TIFA, mechanism controlling NF-κB activation pro-inflammatory gene expression. Here, we compared ability chemically synthesized Shigella flexneri lysate induce TIFA in epithelial cells. In contrast lysate, found fails trigger rapid TIFA. only induces delayed signaling, suggesting it has be processed intracellularly inflammation. By dissecting LPS pathway with deletion mutants functional complementation experiments, show ADP-D-glycero-β-D-manno-heptose ADP-L-glycero-β-D-manno-heptose are bacterial metabolites responsible for oligomerization, they strongly interleukin-8 expression during S. infection. Altogether, our results rule out major role infection identify ADP-heptose new PAMP.