HS increases HMGB1/TLR4 signaling upregulates NOD2 expression in AMϕ, with a subsequent sensitization of AMϕ to NOD2 ligand MDP, which leads to augmented inflammation in the lung. Additionally, upregulated NOD2 signaling induces autophagy in AMϕ, which in turn negatively regulates lung inflammation by suppressing NOD2-RIP2 signaling and inflammasome activation. PMN counteract the anti-inflammatory effect of autophagy, possibly via NAD(P)H oxidase-derived ROS, and therefore enhance post-HS lung inflammation.