Table 1 Common DC subsets and their metabolic requirements

Main function

Antigen cross-presentation to CD8⁺ T cells, IL-12, IL-6 secretion

Direct antigen-presentation to CD4⁺ T cells, IL-6, TNF-α, IL-23 secretion

IFN-I production

Antigen presentation and TNF-α, IL-12, IL-23 secretion

Transcription factors

Batf3, Irf8, Id2

Irf4, Notch2, Klf4

Irf8, E2-2, Irf7

Klf4, Irf8

Surface markers (mouse)

CD11c, MHCII, XCR1, CLEC9A, CD24, DEC205 CD8α (resident), CD103 (migratory)

CD11c, MHCII, SIRPα, CD11b

CD11c^low, MHCII^low, PDCA1, Siglec H, B220. CD209, SIRPα,

CD11c, MHCII, CD11b, Ly6C,CD14, CCR2

Surface markers (human)

CD11c^low, MHCII, XCR1, CLEC9A, CD141, DEC205

CD11c, MHCII, SIRPα, CD1c,

MHCII^low, CD123, CLEC4C, CD304, CCR2

CD11c, MHCII, CD11b CD14, CD1c, CD64, CD206, CD209, SIRPα, CD1a, CCR2

Development and differentiation

PI3K/Akt and mTOR is required for Flt3L-induced DC development^a,c [10] AMPK-KO or FAO-inhibition increase cDC2/cDC1^a,c [11] Mst1/Mst2 deficiency impair Flt3L-expansion of splenic cDC1^c [12]

ROS-inhibition increases cDC1/cDC2^a [11]

PI3K/Akt and mTOR is required for Flt3L-induced DC development^a,c [10]

Increased mitochondrial activity and ROS is required for differentiation into moDCs^d [17] Upregulated mitochondrial biogenesis genes PGC-1α, NRF-1, TFAM^d [18] Constitutive active PI3K/mTOR signaling^d [16]

Steady-state

OXPHOS^high Glycolysis^{high a,c} [11, 12, 19] Glycogen storage^b [167]

OXPHOS^low Glycolysis^{low a,c} [11, 12, 19] Glycogen storage^b [167]

Early Activation

PRR stimulation induces TBK1/IKKε/Akt-dependent glycolysis and FAS^a,b [19, 20, 22, 23] Glycolysis and FAS are required for DC maturation^,c [19, 23] Glycolysis is required for DC migration^b,c [21] Glycogenolysis fuels glycolysis^b [167]

TLR induced glutaminolysis-driven OXPHOS required for pDC IFN-I and co-stimulatory molecules^e [36] IFN-I-induced FAO enhance autocrine IFN-I and pDC function^a [28] Stimuli-dependent reliance on glycolysis for IFN-I production^f [35] mTOR-dependent RLR-induced IFN-I production^f [47]

PRR stimulation induces glycolysis and iNOS expression^b,c [23, 24] Glycogenolysis fuels glycolysis^d [167] mTOR-dependent PRR activation^d [47]

Mature DC

Glucose-deprivation 8 h after LPS enhance CD8⁺ T cell priming^b [44] Mst1/2-dependent IL-12 production and CD8+ T cell priming^,c [12] Lipid bodies promote antigen cross presentation^a [79, 80] Lipid overload diminishes antigen uptake^{d, f} [32, 33] NOX2-produced ROS required for antigen processing and CD8⁺ T cell priming^{b, c} [82, 83]

Contrasting data mTORC1 blocks MHCII expression and antigen uptake^b [42, 69, 70] mTORC1 facilitates MHCII peptide loading ^{b, d} [71, 72]

Glycolysis^high and iNOS required for survival^c [24] mTOR required for antigen uptake^d [45]