TLR4 and injury: It is interesting to note here that a similar modulation of NOD2 signaling by extracellular HMGB1, not cytosolic HMGB1, has been reported in an animal model of acute lung injury, wherein extracellular HMGB1/TLR4 signaling activates NOD2, which induces autophagy and suppresses NOD2-RIP2 signaling [31].