ADP-heptose: A new innate immune modulator.

Lipopolysaccharide (LPS) is a well-known pathogen-associated molecular pattern (PAMP) produced by gram-negative bacteria. Previous studies showed that a key metabolic intermediate in LPS biosynthesis, d-glycero-β-d-manno-heptose 1,7-bisphosphate (HBP), could activate the NF-κB pathway and trigger the innate immune responses. However, it was unclear whether HBP could be a novel PAMP and its pattern recognition receptor (PRR) is not fully understood. Very recently, the Shao group reported that another key metabolic intermediate in LPS biosynthesis, ADP-heptose, could be transported into mammalian cells and bind with ALPK1 (alpha-kinase 1), which leads to a series of strong immune responses. These findings broaden our understanding on bacterial metabolites as a new type of PAMP and these small molecules hold great potential to be applied in the development of novel immune modulators. This minireview focuses on the roles of ADP-heptose related metabolites in innate immunity.