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, LPS 685 increases dimer and tetramer levels of pyruvate-kinase 2 (PKM2), which leads to succinate 686 accumulation. Dimers can translocate into the nucleus

, LPS also alters the 688 tricarboxylic acid (TCA) cycle leading to a reduced level of oxidative phosphorylation 689 (OXPHOS) and subsequent succinate and citrate accumulation, LPS-induction of PKM2 tetramers increases the rate of glycolysis

, In mitochondria, succinate oxidation leads to mitochondrial reactive oxygen species (mROS), p.692

, Accumulated citrate 693 is used to generate nitric oxide (NO), ROS and the antimicrobial metabolite itaconate

, Metabolic changes that benefit pathogenic bacteria (brown arrows) include the induction of 695

, M2 metabolism by Salmonella enterica to have glucose available, a metabolite that is then 696 sequestered inside the bacterial vacuole. Legionella pneumophila-induced alterations of 697 mitochondrial dynamics reduce OXPHOS. Mycobacterium tuberculosis also reduces 698

. Oxphos, DAMMs are detected by inflammasomes such 700 as NOD-like receptor family, pyrin domain containing 3 (NLRP3) (violet arrows), which in 701 turn activates caspases and leads to the production of IL-1? and IL-18