Table 2.

The potential immunometabolic targets of ALI.

Potential drug targets	Molecular Effectors	Function in Immunity	Metabolic Profile	Potential Drugs
NLRP3 inflammasome	glycolytic enzyme HK1, PKM, PFKFB3 NAG-related mtDNA release; TCA cycle metabolites accumulation: succinate fumarate; mitochondrial damage:mtROS mtDNA； NAD + -dependent enzymes SIRT1, 2, 3	promote pyroptosis in macrophage; pro-inflammation phenotype	glycolysis↑ mitochondria damage↑ mtROS↑ NAD+/NADH↓ mtDNA release↑	NLRP3 inhibitor:MCC950 [165]， INF39 [172]，Glyburide [163]，RRx-001[162]
AIM2	glycolysis pathway:GLUT1, PKM2, EIF2AK2 AKT and PP2A AKT/mTOR signaling	pro-inflammatoy macrophage a T cell-intrinsic and inflammasome-independent role in the function of Treg cells	glycolysis ↑/↓ lipid OXPHOS↓	oligodeoxynucleotides (ODNs): ODN-A151 [166]
cGAS-STING axis	HIF-1α S6K1-STING-TBK1 complex mTORC1	repolarize macrophages from M2 to M1; T cell response↑ T-cell proliferation ↓	glycolysis↑ TCA cycle↓ OXPHOS↓ mtROS↑	STING inhibitor: H-151，C-176[167] STING agonist: diABZI [173], DMXAA, cGAMP [174], STING-LNP [175]
AMPK	AMPK/GSK3β-Nrf2 signal AMPK-PPARγ AMPK/SIRT1	repolarize macrophages to M2; neutrophils ↓ Differentiation of Tregs↑	glycolysis↑ gluconeogenesis and glycogen synthesis↓ fatty acid oxidation↑ OXPHOS↑ mitochondria biogenesis↑	AMPK agonist: metformin [159]
mTOR	negative regulated by AMPK； suppressed by ROS accumulation 4EBP1 and P70(S6K) mTOR/HIF-1α autophagy	macrophage activation↑ DCs maturation↑ neutrophil function↑ CD8+ T-cell ↑ Th17 cell differentiation↑ Treg activation↑	protein synthesis and anabolism↑ aerobic glycolysis ↑ autophagy↓	mTOR inhibitors: everolimus [161]，Rapamycin [160]
IRG1	itaconate NRF2 and IκB NLRP3 inflammasome glycolytic enzymes:ALDOA, LDHA, GAPDH TET2 catalytic activity	anti-inflammatory macrophage	succinate accumulation↑ alkylation of protein cysteine residues↑ aerobic glycolysis↓ ferroptosis↓ autophagy↑	itaconate derivatives: 4-octyl itaconate (OI) [169] dimethyl itaconate (DI) [168]
Beta-hydroxybutyrate (BHB)	NLRP3 inflammasome NF-kB-mediated inflammation by binding to HCAR2	IFNγ production↑ CD4+ T cells survival↑ anti-inflammatory macrophage	OXPHOS↑ TCA cycle↑ synthesis of amino acids↑	Beta-hydroxybutyrate (BHB)