Microglial M1/M2 polarization and metabolic states

Ruben Orihuela; Christopher A McPherson; Gaylia Jean Harry

doi:10.1111/bph.13139

journal article May 11, 2015

Microglial M1/M2 polarization and metabolic states

Ruben Orihuela Christopher A McPherson Gaylia Jean Harry

British Journal of Pharmacology Vol. 173 No. 4 pp. 649-665 · Wiley

View at Publisher Save 10.1111/bph.13139

Abstract

Microglia are critical nervous system‐specific immune cells serving as tissue‐resident macrophages influencing brain development, maintenance of the neural environment, response to injury and repair. As influenced by their environment, microglia assume a diversity of phenotypes and retain the capability to shift functions to maintain tissue homeostasis. In comparison with peripheral macrophages, microglia demonstrate similar and unique features with regards to phenotype polarization, allowing for innate immunological functions. Microglia can be stimulated by LPS or IFN‐γ to an M1 phenotype for expression of pro‐inflammatory cytokines or by IL‐4/IL‐13 to an M2 phenotype for resolution of inflammation and tissue repair. Increasing evidence suggests a role of metabolic reprogramming in the regulation of the innate inflammatory response. Studies using peripheral immune cells demonstrate that polarization to an M1 phenotype is often accompanied by a shift in cells from oxidative phosphorylation to aerobic glycolysis for energy production. More recently, the link between polarization and mitochondrial energy metabolism has been considered in microglia. Under these conditions, energy demands would be associated with functional activities and cell survival and thus, may serve to influence the contribution of microglia activation to various neurodegenerative conditions. This review examines the polarization states of microglia and their relationship to mitochondrial metabolism. Additional supporting experimental data are provided to demonstrate mitochondrial metabolic shifts in primary microglia and the BV‐2 microglia cell line induced under LPS (M1) and IL‐4/IL‐13 (M2) polarization.Linked ArticlesThis article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2016.173.issue-4

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References

205

[1]

10.1084/jem.169.3.1021

[2]

10.1111/bph.12451

[3]

10.1111/bph.12445

[4]

10.1111/bph.12449

[5]

10.1016/s0165-3806(99)00113-3

[6]

10.1084/jem.20070075

[7]

10.1126/science.1142883

[8]

10.1016/s1471-4906(02)02223-8

[9]

10.1371/journal.pone.0080908

[10]

10.4049/jimmunol.181.6.3733

[11]

10.1371/journal.ppat.1000066

[12]

10.1002/pmic.200900195

[13]

Endotoxin tolerance: new mechanisms, molecules and clinical significance

Subhra K. Biswas, Eduardo López-Collazo

Trends in Immunology 10.1016/j.it.2009.07.009

[14]

10.1016/j.cmet.2011.11.013

[15]

10.1007/s11481-013-9435-y

[16]

Review: Activation patterns of microglia and their identification in the human brain

D. Boche, V. H. Perry, J. A. R. Nicoll

Neuropathology and Applied Neurobiology 10.1111/nan.12011

[17]

10.2174/1381612043452910

[18]

10.1016/j.freeradbiomed.2014.07.033

[19]

10.1182/blood.v99.9.3427

[20]

10.1073/pnas.87.2.682

[21]

10.1016/0165-5728(94)90109-0

[22]

10.1002/(sici)1097-4547(19991001)58:1<191::aid-jnr17>3.0.co;2-e

[23]

10.1002/jlb.67.1.97

[24]

10.1073/pnas.0604681103

[25]

10.1111/j.1471-4159.2007.04588.x

[26]

10.1038/nn1715

[27]

10.1111/j.1600-065x.2006.00441.x

[28]

Chen CC "Amelioration of LPS‐induced inflammation response in microglia by AMPK activation" BioMed Red Int'l (2014)

[29]

Sterile inflammation: sensing and reacting to damage

Grace Y. Chen, Gabriel Núñez

Nature Reviews Immunology 10.1038/nri2873

[30]

10.1046/j.1471-4159.2002.00864.x

[31]

10.1186/1742‐2094‐11‐98

[32]

10.3389/fimmu.2014.00594

[33]

10.1016/j.bbi.2013.02.005

[34]

10.2174/187152710791012053

[35]

10.1007/s11481-009-9164-4

[36]

10.1038/cr.2011.9

[37]

10.1371/journal.pone.0086660

[38]

10.1038/nn.3668

[39]

10.1016/j.clinbiochem.2013.04.027

[40]

10.1038/nn1472

[41]

10.4049/jimmunol.1103180

[42]

10.1002/glia.22298

[43]

10.1038/ni.1671

[44]

10.1155/2013/541259

[45]

10.1016/j.mcn.2012.10.008

[46]

10.1182/blood-2012-03-419747

[47]

10.1038/ni.2833

[48]

10.1016/j.bbi.2011.10.003

[49]

10.1186/1742‐2094‐7‐45

[50]

10.1126/science.1117729

Showing 50 of 205 references

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Details

Published: May 11, 2015
Vol/Issue: 173(4)
Pages: 649-665
License: View

Authors

R

Ruben Orihuela

Neurotoxicology Group, National Toxicology Program Laboratory National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park NC USA

C

Christopher A McPherson

Neurotoxicology Group, National Toxicology Program Laboratory National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park NC USA

G

Gaylia Jean Harry

Neurotoxicology Group, National Toxicology Program Laboratory National Institute of Environmental Health Sciences, National Institutes of Health Research Triangle Park NC USA

Funding

Division National Toxicology Program, National Institute of Environmental Health Sciences Award: 1Z01ES101623

Cite This Article

Ruben Orihuela, Christopher A McPherson, Gaylia Jean Harry (2015). Microglial M1/M2 polarization and metabolic states. British Journal of Pharmacology, 173(4), 649-665. https://doi.org/10.1111/bph.13139

Microglial M1/M2 polarization and metabolic states

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