Table 1.

Immunometabolism and its change in immune cells during ALI.

	M1 Macrophage	M2 Macrophage	Neutrophils	DCs	NK cells	T cells	B cells
Glycosis	↑ exert pro-inflammatory properties		↑derivation of most energy indispensible for NET formation or chromatin decondensation	↑ initiate glycolysis by utilizing stored glycogen rather than FAO, which depends on PI3K/Akt signal and promotes maturation of DCs	↑lactate dehydrogenase A (LDHA)-deficient NK cells fail to display optimal antiviral effects	↑glucose transporter 1 (GLUT1) is important in differentiation of CD4+ T cell ↑glycosis is important for Th17 cells via epigenetic remodeling such as GLUT3-dependent acetyl-CoA generation	glycolysis mainly offers energy in B1 B cells
							glycolysis promotes B cells to produce antibodies including IgG, IgM, and IgA
PPP	↑ generate NADPH, which is essential for cholesterol metabolism and the synthesis of pro-inflammatory lipid mediators	The carbohydrate kinase-like protein CARKL shifts macrophage to M2 phenotype via PPP	activated glucose-6-phosphate dehydrogenase (G6PD) enhances NADPH production and NET formation	↑			glucose acts as the ingredient of ribonucleotide synthesis in naïve B cells
TCA	Fumarate accumulation, which induces monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases		Succinate accumulation, which stabilizes of HIF-1α and enhance glycolysis				TCA cycle produces main energy in naïve B cells
	Citrate accumulation, which generates fatty acids, serving as important ingredient for prostaglandin production membrane biogenesis
	Succinate accumulation, which upregulates glycolytic enzymes and pro-inflammatory IL-1β
Lipid metabolism	↓ Blocked triglyceride lipolysis Triglyceride accumulation	↑FAO increase The scavenger receptor CD36-mediated uptake of triacylglycerol substrates and lysosomal lipolysis		↑upregulated PPARγ and increased citrate synthase activity,which induced fatty acid synthesis and promote DC differentiation	↑glycerolipid metabolism including LPIN1 and LPIN2 that increases the level of intracellular calcium and facilitates NK cell cytotoxicity	enhanced cytidine diphosphate (CDP) –ethanolamine pathway could promotes its migration via stabilizing the CXCR5 on the T cell surface	B2 B cells rely on FAO for their energy demand, which will shift to glycolysis by increasing GLUT1-mediated glucose uptake and mTORC1 and c-Myc expression upon activation
						short-chain fatty acids (SCFAs) like butyrate enhance mitochondrial and glycolytic metabolism， promoting anti-influenza immunity in CD8+ T; trigger T cell differentiation by inducing NETs during ALI.
						Fatty acis synthesis are required for the function of Th17 cells and fatty acid oxidation for Treg
Amino acid metabolism	↑Glutamine: a source of citrate for fatty acid synthesis or be used for ATP production, thus feeding TCA cycle glutamine is essential for IL-1β secretion					leucine, methionine, glutamine, together with their transporters could promote terminal effector (Teff) cells proliferation and survival，which expressed higher amount in activated CD8+ T cell than CD4+ T cells	glutaminolysis accompanied by glycosis through an elevation in mTORC1 and c-Myc expression
	Tryptophan: anabolic growth and cellular proliferation Arginine: also produces NO
						↓arginine as well as its metabolites display a pronounced reduction, which may possibly impede normal Tmem or Teff responses during COVID-19
						glutaminolysis is important for Th17 cells
Mitochondria metabolism	↓inhibitory OXPHOS		very few functional mitochondria in mature neutrophils; lower levels of OXPHOS complexes and mitochondrial enzymes involving fumarase and glutamate dehydrogenase (GDH)	↑upregulated PPARγ and PGC1α that is responsible for mitochondrial biogenesis during DCs differentiation		↑ mitochondrial pro-fission protein Drp1 directs T cells trafficking to migration and expansion
			Mitochondrial electron transport chain at Complex III functions in NET formation; Impaired complex III, IV and V are associated with dysfunction of LPS-driven neutrophil chemotaxis	↑Inhibiting mitochondrial respiration suppresses DCs differentiation
						redistrubution of P2Y11 receptor signaling which shuts down the activation of nearby mitochondria and P2X4 receptor where mitochondrial ATP production amplifies needed for pseudopod protrusion and T cell migration.
others					↑ inositol phosphate metabolism including phospholipase C γ 2 (PLCG2) that mobilizes intracellular calcium and secretes cytotoxic granules	Many selective transcription factors including IRF4, SREBPs, MYC, and NFAT are necessary for anabolism and T cell function
						inositol phosphate and glycerolipid metabolism enhance cytotoxicity of CD8+ T cells
						enhanced glycosaminoglycan metabolism, which is associated with CD8+ Teff cell↑ and CD8+ Tmem↓