Figure 3.

M1 macrophage defenses upon bacterial infection. In M1 macrophages, the mitochondrial TCA cycle is shunted at the isocitrate dehydrogenase (IDH) step, subsequently leading to itaconate formation. The succinate dehydrogenase (SDH) step is also arrested, leading to succinate accumulation and IL-1β transcription increase in a Hif1-α-dependent manner. Decrease in TCA cycle activity efficiency is also responsible for an increase in ΔΨ_m that induces the production of mROS. In bacteria-infected macrophages (left part), phagosomal maturation is responsible for N-acetylglucosamine (GlcNAc) release. GlcNAc binds mitochondrial hexokinase (HK) and induces its cytosolic release that activates NLRP3 inflammasome. mROS also induce NLRP3 activation.