Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS–) vs. Alternatively Activated Macrophages

Macrophages are found in tissues, body cavities, and mucosal surfaces. Most tissue macrophages are seeded in the early embryo before definitive hematopoiesis is established. Others are derived from blood monocytes. The macrophage lineage diversification and plasticity are key aspects of their functi...

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Published in:Frontiers in immunology Vol. 10; p. 1084
Main Authors: Orecchioni, Marco, Ghosheh, Yanal, Pramod, Akula Bala, Ley, Klaus
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 24.05.2019
Subjects:
Animals
Arginine - metabolism
cancer
Cell Movement
Cell Polarity
Chemotaxis
Humans
Immunology
innate immunity
Lipid Metabolism
Lipopolysaccharides - pharmacology
macrophage
Macrophage Activation - physiology
Macrophages - physiology
Mice
Protein Processing, Post-Translational
Signal Transduction
macrophage
cancer
M1
innate immunity
M2
ISSN:1664-3224, 1664-3224
Online Access:Get full text
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Summary:Macrophages are found in tissues, body cavities, and mucosal surfaces. Most tissue macrophages are seeded in the early embryo before definitive hematopoiesis is established. Others are derived from blood monocytes. The macrophage lineage diversification and plasticity are key aspects of their functionality. Macrophages can also be generated from monocytes and undergo classical (LPS+IFN-γ) or alternative (IL-4) activation. , macrophages with different polarization and different activation markers coexist in tissues. Certain mouse strains preferentially promote T-helper-1 (Th1) responses and others Th2 responses. Their macrophages preferentially induce iNOS or arginase and have been called M1 and M2, respectively. In many publications, M1 and classically activated and M2 and alternatively activated are used interchangeably. We tested whether this is justified by comparing the gene lists positively [M1(=LPS+)] or negatively [M2(=LPS-)] correlated with the ratio of and in transcriptomes of LPS-treated peritoneal macrophages with classically (LPS, IFN-γ) vs. alternatively activated (IL-4) bone marrow derived macrophages, both from published datasets. Although there is some overlap between M1(=LPS+) and classically activated (LPS+IFN-γ) and M2(=LPS-) and alternatively activated macrophages, many more genes are regulated in opposite or unrelated ways. Thus, M1(=LPS+) macrophages are not equivalent to classically activated, and M2(=LPS-) macrophages are not equivalent to alternatively activated macrophages. This fundamental discrepancy explains why most surface markers identified on generated macrophages do not translate to the situation. Valid M1/M2 surface markers remain to be discovered.
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Edited by: Liwu Li, Virginia Tech, United States
This article was submitted to Molecular Innate Immunity, a section of the journal Frontiers in Immunology
Reviewed by: Inger Øynebråten, Oslo University Hospital, Norway; Christos Tsatsanis, University of Crete, Greece
Present address: Klaus Ley, Division of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA, United States
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.01084