. 2021 Dec 7;19(3):384–408. doi: 10.1038/s41423-021-00791-9

Table 1.

Overview of the main functions and metabolic features of tissue macrophage populations

Macrophage type	Organ/system	Ontogeny	Main surface markers	Main functions	Main metabolic features	References
Alveolar macrophages	Lung	Fetal liver monocytes	CD11c⁺ SiglecF⁺ CXC3R1⁻	Surfactant clearance, phagocytosis of inhaled particles, immune sentinel functions	↑OXPHOS/mitochondrial respiration, lipid catabolism, cholesterol handling (PPARγ, LXRα, C/EBPβ, VHL); ↓Glycolysis	[5, 6, 65–70, 74–83, 85–88]
Interstitial macrophages	Lung	Adult bone marrow/blood monocytes	CXC3R1⁺ CD11b⁺ SiglecF⁻	Control of pathogens and infections, immune sentinel functions	Upon Mtb infection: ↑Glycolysis; ↓Mitochondrial respiration, fatty acid or cholesterol metabolism	[5, 65, 87, 88]
Marginal zone macrophages	Spleen	Adult bone marrow/blood monocytes	SIGNR1⁺	Removal of blood-borne antigens and pathogens	Their development and immune function is controlled by LXRα (and LXRβ)	[89–93]
Marginal metallophilic macrophages	Spleen	Adult bone marrow/blood monocytes	CD169⁺ Sialoadhesin⁺	Removal of blood-borne antigens and pathogens	Their development and immune function is controlled by LXRα (and LXRβ)	[89–93]
Tingible body macrophages	Spleen	Adult bone marrow/blood monocytes	F4/80⁻ CD68⁺	B cell phagocytosis during germinal center reaction	To be investigated	[89, 90]
Red pulp macrophages	Spleen	Yolk sac and fetal liver progenitors	F4/80⁺ VCAM1⁺ CD11b^lo	Clearance of erythrocytes, platelets and blood pathogens; iron recycling; immune sentinel functions	↑Iron metabolism (Spi-C, NRF2, HO-1), lipid and cholesterol handling (PPARγ, LXRα)	[3, 4, 66, 70, 89, 90, 95,99–107]
Liver capsular macrophages	Liver	Adult bone marrow/blood monocytes	F4/80⁺ CX3CR1⁺ MHCII⁺	Immune surveillance, neutrophil recruitment	↓Metabolic gene signatures compared with Kupffer cells	[94, 95, 98]
Kupffer cells	Liver	Fetal liver monocytes	F4/80⁺ Clec4F⁺ Tim4⁺	Clearance of erythrocytes and blood pathogens; iron metabolism; mediators of immunological tolerance	↑Iron metabolism (Spi-C, NRF2, HO-1), lipid and cholesterol handling (PPARγ, LXRα); ↓Glycolysis (upregulated upon stimulation)	[3, 4, 7, 70, 91, 94–104, 106, 107, 109]
Erythroid island macrophages	Bone marrow	Adult bone marrow and fetal liver (likely)	F4/80⁺ VCAM1⁺ CD169⁺	Support of erythropoiesis, iron handing	↑Iron metabolism (Spi-C, HO-1) and fatty acid metabolism signatures	[106, 107]
Small peritoneal macrophages	Peritoneum	Adult bone marrow/blood monocytes	F4/80-low CD11b-low MHCII-hi	Immune sentinel functions and inflammatory regulation	↑Glycolysis and OXPHOS upon activation compared with large peritoneal macrophages	[110, 111]
Large peritoneal macrophages	Peritoneum	Yolk sac progenitors	F4/80^hi CD11b^hi MHCII^lo	Clearance of dead cells/bacteria, inflammatory regulation, antimicrobial defense	Naïve: ↑ETC/CII, ROS, lipid and cholesterol handling (GATA6, C/EBPβ, RXRα/β) Stimulated: context-dependent OXPHOS; ↓Lipid metabolism/FAO; ↑Glycolysis	[70, 78–80, 86, 110–120]
Microglia	Central nervous system	Yolk sac progenitors	F4/80⁺ CX3CR1⁺ CD11b⁺	Immune sentinel functions; clearance of apoptotic cells; regulation of brain homeostasis, neurogenesis and synaptic activity	Naïve: ↑OXPHOS, context-dependent fuel use (mainly glucose) and metabolic pathway activation Stimulated: ↑Glycolysis; ↓OXPHOS	[121–126]
Osteoclasts	Bone marrow, spleen, blood	Adult bone marrow/blood monocytes	TRAP⁺ (tartrate- resistant acid phosphatase)	Bone resorption (dissolution of collagen and mineralized bone)	Naïve: ↑OXPHOS/CI activity, FAO, glutaminolysis Bone-exposed: ↑Glycolysis, HIF-1α, lactate production	[128–135]
Intestinal lamina propria macrophages	Intestine	Adult bone marrow/blood monocytes	CD64⁺ MHCII^hi CD206⁺	Clearance of dead cells, maintenance of epithelial homeostasis, immune sentinel functions, antimicrobial activity	Butyrate-exposed: ↑ROS production; Unaltered OXPHOS; ↓Glycolysis and mTOR signaling	[136–138]
Kidney-resident macrophages	Kidney	Yolk sac and/or fetal liver progenitors	CD64⁺ F4/80⁺ CD11c⁺	Clearance of dead cells, likely regulation of ureteric bud branching and vascular development	↑Fatty acid metabolism-, ↓OXPHOS- and glycolysis-related gene expression (healthy compared with lupus-like disease)	[116, 139, 140]
White adipose tissue macrophages	Lean white adipose tissue	Yolk sac progenitors (predominantly)	F4/80⁺ CD11b⁺ CD206⁺	Efferocytosis and apoptotic cell clearance	Metabolically quiescent (↓Glycolysis and ↓OXPHOS compared with macrophages from obese fat)	[189, 191, 196]
Embryonic cardiac macrophages	Heart	Yolk sac and fetal liver progenitors	CD64⁺ CX3CR1⁺	Efferocytosis and immune sentinel functions	Metabolically quiescent (↓Glycolysis and ↓OXPHOS compared with macrophages upon MI)	[141, 146]
Monocyte-derived cardiac macrophages	Heart	Adult bone marrow/blood monocytes	CCR2⁺ MerTK⁺ CD64⁺ CD11c^hi CD206⁺	Immune surveillance	↑Glycolysis upon MI; ↑OXPHOS and ↓Glycolysis from Day 3 after MI.	[67, 141, 146]
Skeletal muscle macrophages	Skeletal muscle	Embryonic and bone marrow precursors	CD11b⁺ F4/80⁺ CD64⁺	Maintenance of tissue homeostasis, muscle growth and regeneration	To be investigated	[145]