Metabolic Adaption of Mucosal Macrophages: Is Metabolism a Driver of Persistence Across Tissues?

Overview

Journal Mucosal Immunol

Publisher Elsevier

Specialty Allergy & Immunology

Date 2023 Jun 29

PMID 37385586

Authors

Clare L Bennett

Georgia Perona-Wright

Affiliations

Soon will be listed here.

Abstract

Macrophages play essential roles in tissue homeostasis, defense, and repair. Their functions are highly tissue-specific, and when damage and inflammation stimulate repopulation by circulating monocytes, the incoming monocytes rapidly acquire the same, tissue-specific functions as the previous, resident macrophages. Several environmental factors are thought to guide the functional differentiation of recruited monocytes, including metabolic pressures imposed by the fuel sources available in each tissue. Here we discuss whether such a model of metabolic determinism can be applied to macrophage differentiation across barrier sites, from the lung to the skin. We suggest an alternative model, in which metabolic phenotype is a consequence of macrophage longevity rather than an early driver of tissue-specific adaption.

Citing Articles

Macrophage-induced enteric neurodegeneration leads to motility impairment during gut inflammation.

Bresser M, Siemens K, Schneider L, Lunnebach J, Leven P, Glowka T EMBO Mol Med. 2025; 17(2):301-335.

PMID: 39762650 PMC: 11822118. DOI: 10.1038/s44321-024-00189-w.

References

Allen J . IL-4 and IL-13: Regulators and Effectors of Wound Repair. Annu Rev Immunol. 2023; 41:229-254. DOI: 10.1146/annurev-immunol-101921-041206. View

Bonnardel J, TJonck W, Gaublomme D, Browaeys R, Scott C, Martens L . Stellate Cells, Hepatocytes, and Endothelial Cells Imprint the Kupffer Cell Identity on Monocytes Colonizing the Liver Macrophage Niche. Immunity. 2019; 51(4):638-654.e9. PMC: 6876284. DOI: 10.1016/j.immuni.2019.08.017. View

Aegerter H, Kulikauskaite J, Crotta S, Patel H, Kelly G, Hessel E . Influenza-induced monocyte-derived alveolar macrophages confer prolonged antibacterial protection. Nat Immunol. 2020; 21(2):145-157. PMC: 6983324. DOI: 10.1038/s41590-019-0568-x. View

Schneider C, Nobs S, Kurrer M, Rehrauer H, Thiele C, Kopf M . Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages. Nat Immunol. 2014; 15(11):1026-37. DOI: 10.1038/ni.3005. View

Pan Y, Tian T, Park C, Lofftus S, Mei S, Liu X . Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature. 2017; 543(7644):252-256. PMC: 5509051. DOI: 10.1038/nature21379. View

Vrieling F, Kostidis S, Spaink H, Haks M, Mayboroda O, Ottenhoff T . Analyzing the impact of Mycobacterium tuberculosis infection on primary human macrophages by combined exploratory and targeted metabolomics. Sci Rep. 2020; 10(1):7085. PMC: 7184630. DOI: 10.1038/s41598-020-62911-1. View

Ginhoux F, Guilliams M . Tissue-Resident Macrophage Ontogeny and Homeostasis. Immunity. 2016; 44(3):439-449. DOI: 10.1016/j.immuni.2016.02.024. View

Violante S, Berisa M, Thomas T, Cross J . Stable Isotope Tracers for Metabolic Pathway Analysis. Methods Mol Biol. 2019; 1978:269-283. DOI: 10.1007/978-1-4939-9236-2_17. View

Grainger J, Konkel J, Zangerle-Murray T, Shaw T . Macrophages in gastrointestinal homeostasis and inflammation. Pflugers Arch. 2017; 469(3-4):527-539. PMC: 5362667. DOI: 10.1007/s00424-017-1958-2. View

10.

Do T, Ma F, Andrade P, Teles R, Silva B, Hu C . TREM2 macrophages induced by human lipids drive inflammation in acne lesions. Sci Immunol. 2022; 7(73):eabo2787. PMC: 9400695. DOI: 10.1126/sciimmunol.abo2787. View

11.

Denning T, Norris B, Medina-Contreras O, Manicassamy S, Geem D, Madan R . Functional specializations of intestinal dendritic cell and macrophage subsets that control Th17 and regulatory T cell responses are dependent on the T cell/APC ratio, source of mouse strain, and regional localization. J Immunol. 2011; 187(2):733-47. PMC: 3131424. DOI: 10.4049/jimmunol.1002701. View

12.

Kolter J, Feuerstein R, Zeis P, Hagemeyer N, Paterson N, dErrico P . A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves. Immunity. 2019; 50(6):1482-1497.e7. DOI: 10.1016/j.immuni.2019.05.009. View

13.

Kaplan D, Li M, Jenison M, Shlomchik W, Flavell R, Shlomchik M . Autocrine/paracrine TGFbeta1 is required for the development of epidermal Langerhans cells. J Exp Med. 2007; 204(11):2545-52. PMC: 2118472. DOI: 10.1084/jem.20071401. View

14.

Bain C, Bravo-Blas A, Scott C, Gomez Perdiguero E, Geissmann F, Henri S . Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nat Immunol. 2014; 15(10):929-937. PMC: 4169290. DOI: 10.1038/ni.2967. View

15.

Wculek S, Dunphy G, Heras-Murillo I, Mastrangelo A, Sancho D . Metabolism of tissue macrophages in homeostasis and pathology. Cell Mol Immunol. 2021; 19(3):384-408. PMC: 8891297. DOI: 10.1038/s41423-021-00791-9. View

16.

Wang A, Luan H, Medzhitov R . An evolutionary perspective on immunometabolism. Science. 2019; 363(6423). PMC: 6892590. DOI: 10.1126/science.aar3932. View

17.

Seneschal J, Clark R, Gehad A, Baecher-Allan C, Kupper T . Human epidermal Langerhans cells maintain immune homeostasis in skin by activating skin resident regulatory T cells. Immunity. 2012; 36(5):873-84. PMC: 3716276. DOI: 10.1016/j.immuni.2012.03.018. View

18.

Scott C, Zheng F, De Baetselier P, Martens L, Saeys Y, De Prijck S . Bone marrow-derived monocytes give rise to self-renewing and fully differentiated Kupffer cells. Nat Commun. 2016; 7:10321. PMC: 4737801. DOI: 10.1038/ncomms10321. View

19.

Chiaranunt P, Tai S, Ngai L, Mortha A . Beyond Immunity: Underappreciated Functions of Intestinal Macrophages. Front Immunol. 2021; 12:749708. PMC: 8506163. DOI: 10.3389/fimmu.2021.749708. View

20.

Gosselin D, Link V, Romanoski C, Fonseca G, Eichenfield D, Spann N . Environment drives selection and function of enhancers controlling tissue-specific macrophage identities. Cell. 2014; 159(6):1327-40. PMC: 4364385. DOI: 10.1016/j.cell.2014.11.023. View