» Articles » PMID: 27459405

A Polarizing Question: Do M1 and M2 Microglia Exist?

Overview
Journal Nat Neurosci
Date 2016 Jul 27
PMID 27459405
Citations 808
Authors
Affiliations
Soon will be listed here.
Abstract

Microglial research has entered a fertile, dynamic phase characterized by novel technologies including two-photon imaging, whole-genome transcriptomic and epigenomic analysis with complementary bioinformatics, unbiased proteomics, cytometry by time of flight (CyTOF; Fluidigm) cytometry, and complex high-content experimental models including slice culture and zebrafish. Against this vivid background of newly emerging data, investigators will encounter in the microglial research literature a body of published work using the terminology of macrophage polarization, most commonly into the M1 and M2 phenotypes. It is the assertion of this opinion piece that microglial polarization has not been established by research findings. Rather, the adoption of this schema was undertaken in an attempt to simplify data interpretation at a time when the ontogeny and functional significance of microglia had not yet been characterized. Now, terminology suggesting established meaningful pathways of microglial polarization hinders rather than aids research progress and should be discarded.

Citing Articles

Do microglia metabolize fructose in Alzheimer's disease?.

Sturno A, Hassell Jr J, Lanaspa M, Bruce K J Neuroinflammation. 2025; 22(1):85.

PMID: 40089786 DOI: 10.1186/s12974-025-03401-x.


Esketamine attenuates traumatic brain injury by modulating STAT3-mediated Glycolysis and immune responses.

Liu Y, Gong Z, Zhang L, Yang X, Zhu J, Zhou X BMC Neurosci. 2025; 26(1):21.

PMID: 40055623 PMC: 11889827. DOI: 10.1186/s12868-025-00941-z.


Sex differences in the microglial response to stress and chronic alcohol exposure in mice.

Soares A, Garcia-Rivas V, Fai C, Thomas M, Zheng X, Picciotto M Biol Sex Differ. 2025; 16(1):19.

PMID: 40038827 PMC: 11881309. DOI: 10.1186/s13293-025-00701-y.


Transcriptomic profiling identifies ferroptosis and NF-κB signaling involved in α-dimorphecolic acid regulation of microglial inflammation.

Zhu X, Wang P, Chao S, Tang W, Zhao L, Yu L J Transl Med. 2025; 23(1):260.

PMID: 40038710 PMC: 11877847. DOI: 10.1186/s12967-025-06296-7.


Microglial Mechanisms and Therapeutic Potential in Brain Injury Post-Intracerebral Hemorrhage.

Gong Y, Li H, Cui H, Gong Y J Inflamm Res. 2025; 18:2955-2973.

PMID: 40026311 PMC: 11872102. DOI: 10.2147/JIR.S498809.


References
1.
Viader A, Ogasawara D, Joslyn C, Sanchez-Alavez M, Mori S, Nguyen W . A chemical proteomic atlas of brain serine hydrolases identifies cell type-specific pathways regulating neuroinflammation. Elife. 2016; 5:e12345. PMC: 4737654. DOI: 10.7554/eLife.12345. View

2.
Morganti J, Riparip L, Rosi S . Call Off the Dog(ma): M1/M2 Polarization Is Concurrent following Traumatic Brain Injury. PLoS One. 2016; 11(1):e0148001. PMC: 4726527. DOI: 10.1371/journal.pone.0148001. View

3.
Link V, Gosselin D, Glass C . Mechanisms Underlying the Selection and Function of Macrophage-Specific Enhancers. Cold Spring Harb Symp Quant Biol. 2015; 80:213-21. PMC: 4936825. DOI: 10.1101/sqb.2015.80.027367. View

4.
Martinez F, Gordon S . The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014; 6:13. PMC: 3944738. DOI: 10.12703/P6-13. View

5.
Alliot F, Godin I, Pessac B . Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res. 1999; 117(2):145-52. DOI: 10.1016/s0165-3806(99)00113-3. View