Cathepsin B is potent to directly interact with NLRP3 at the ER levels, resulting in pyroptosome formation and pro-caspase-1 activation.191 As demonstrated in sepsis model, neutrophil extracellular trap (NET)-derived HMGB1 was indicated as the distinct source for caspase-1-dependent macrophage pyroptosis associated with augmented pro-inflammatory activities.192. Here, HMGB1 is linked to Sepsis.