Table 2.

Toll-like receptor 4 agonist mediated augmentations in mitochondrial metabolism and immunoregulation

Metabolite	Immunomodulatory Effect	Reference(s)
MALATE (Via ↑ production and shuttling back into the mitochondria)	Associated with ↑ TCA flux cycle, ↑ oxygen consumption rate, & ↑ phagocytic capacity	Fensterheim et.al. J Immunol 2018 [36]
CITRATE (Via ↑ accumulation via downregulation of IDH)	↑ Expression of mitochondrial citrate carrier, ↑ Export to cytosol, downstream inflammatory response	Infantino et. al. Biochem J 2011 [105]
	↑ Itaconate	Jha et. al. Immunity 2015 [104]
ITACONATE (Via accumulation of citrate and ↑ Irg1)	Antiinflammatory
	↑ Nrf2, heme oxygenase 1, glutathione	Mills et. al. Nature 2018 [111]
	↓ IL-1β, IL-6	Bambouskova et.al. Nature 2018 [112]
	↓ SDH activity (↓ proinflammatory cytokines, ↓ ROS)	Lampropoulou et. al.Cell Metab 2016 [114]
	Antimicrobial
	Inhibition of Microbial glyoxalate shunt	Cordes et. al. Annu Rev Nutr 2015 [115]
	Inhibits microbial growth	Michelucci et. al.PNAS 2013 [109]
		Sasikaran et. al.Nat Chem Biol 2014 [116]
SUCCINATE (Via downregulation of SDH and glutamine anapleurosis)	↑ IL-1β, inflammation,	Tannahill et. al. Nature 2013 [99]
	HIF-1α stabilization	Mills et. al. Trends Cell Biol 2014 [118]
	Succinylation of target proteins via ↓ SIRT5	Tannahill et. al. Nature 2013 [99]
	↑ mitochondrial ROS generation	Chouchani et. al. Cell Metab 2016 [121]