Cited by 1,259Immune cells in cancerImmune responses and vaccinationsImmune Response and Inflammation

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Macrophage Polarization Comes of Age

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Mantovani,, Alberto, Sica,, Antonio, Locati, Massimo·2005·Immunity

DOI 10.1016/j.immuni.2005.10.001

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Abstract

Functional polarization of macrophages into M1 or M2 cells is an operationally useful, simplified conceptual framework describing the plasticity of mononuclear phagocytes. Genetic approaches have begun to shed new light on mechanisms underlying macrophage polarization and on the actual in vivo significance of polarized M2 cells ( [this issue of Immunity]).

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The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534
Self-citation
Alternative activation of macrophages
Gordon, S. (2003) · Nature Reviews Immunology · doi:10.1038/nri978 · Cited by 6,189
Fibrotic disease and the TH1/TH2 paradigm
Wynn, T. A. (2004) · Nature Reviews Immunology · doi:10.1038/nri1412 · Cited by 1,765

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Background
RETRACTED: The cross-talk between tumor-associated macrophages and tumor endothelium: Recent advances in macrophage-based cancer immunotherapy
Baradaran, A., Asadzadeh, Z., Hemmat, N., Baghbanzadeh, A., Shadbad, M. A., Khosravi, N., Derakhshani, A., Alemohammad, H., Nour, M. A., Safarpour, H., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.112588 · Cited by 37
Retracted
Essential Role of IL-12 in Angiogenesis in Type 2 Diabetes
Ali, M., Mali, V., Haddox, S., Abdel-Ghany, S. M., El-Deek, S. E. M., Abulfadl, A., Matrougui, K., & Belmadani, S. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2017.07.021 · Cited by 33
“29,40 IFN-g biases M1 polarization, 41,42 which could explain the inhibitory effect of IL-12 on angiogenesis in type 2 diabetes.”
Background
Interleukin-1 Receptor-associated Kinase-4 (IRAK4) Promotes Inflammatory Osteolysis by Activating Osteoclasts and Inhibiting Formation of Foreign Body Giant Cells
Katsuyama, E., Miyamoto, H., Kobayashi, T., Sato, Y., Wu, H., Kanagawa, H., Fujie, A., Tando, T., Watanabe, R., Morita, M., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.568360 · Cited by 39
“Macrophages consist of two major subpopulations, M1 and M2 (24, 25).”
Background
Epidermal Growth Factor Receptor (EGFR) Signaling Is a Key Mediator of Hormone-Induced Leukocyte Infiltration in the Pubertal Female Mammary Gland
Aupperlee, M. D., Zhao, Y. M., Tan, Y., Leipprandt, J. R., Bennett, J. M., Haslam, S. Z., & Schwartz, R. C. (2014) · Endocrinology · doi:10.1210/en.2013-1933 · Cited by 32
Flagellin or Lipopolysaccharide Treatment Modified Macrophage Populations after Colorectal Radiation of Rats
Lacavé-Lapalun, J.-V., Benderitter, M., & Linard, C. (2013) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.113.204040 · Cited by 40
“associated with expression of a particular set of cytokines and chemokines (Mantovani et al., 2005).”
Background
Alzheimer's disease risk alleles in TREM2 illuminate innate immunity in Alzheimer's disease
Golde, T. E., Streit, W. J., & Chakrabarty, P. (2013) · Alzheimer s Research & Therapy · doi:10.1186/alzrt178 · Cited by 39
“A potentially useful framework to classify innate immune activation states that was adopted from studies of peripheral macrophages has been to describe microglial phenotype as a classic activation (M1) or alternative activation (M2) state [38-40].”
Lentiviral Vectors: A Versatile Tool to Fight Cancer
Emeagi, P. U., Goyvaerts, C., Maenhout, S. K., Pen, J. J., Thielemans, K., & Breckpot, K. (2013) · Current Molecular Medicine · doi:10.2174/1566524011313040011 · Cited by 31
“In response to different environmental signals, myeloid cells can switch on different functional programs [56, 57].”
Background
Tumor Immuno-Environment in Cancer Progression and Therapy
Kaliński, P., & Talmadge, J. E. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-67577-0_1 · Cited by 49
Bidirectional regulation of the cGAS-STING pathway in the immunosuppressive tumor microenvironment and its association with immunotherapy
Zhang, Y., Wang, Y., Mu, P., Zhu, X. G., & Dong, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1470468 · Cited by 24
Immune Cycle‐Based Strategies for Cancer Immunotherapy
Li, Y., Liu, X., Zhang, X., Pan, W., Li, N., & Tang, B. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202107540 · Cited by 42
Multi‐omics analysis of tumor mutational burden combined with prognostic assessment in epithelial ovarian cancer based on TCGA database
Liu, J., Xu, W., Li, S., Sun, R., & Cheng, W. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.50491 · Cited by 35
“Interferon-γ could induce the differentiation of M1 macrophages, and the M1 macrophages produce high levels of interleukin (IL)-12, IL-23, TNF-a, IL-1, IL-6, reactive oxygen and nitrogen intermediates, as well as other effector molecules [36-38].”
Background
Potential Therapeutic Strategies for Intracranial Aneurysms Targeting Aneurysm Pathogenesis
Liu, Z.-Z., Ajimu, K., Yalikun, N., Zheng, Y., & Xu, F. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.01238 · Cited by 32
Effect of chronic inflammation and immune response on regeneration induced by decellularized bovine pericardium
Umashankar, P. R., Arun, T., & Kumary, T. V. (2012) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.34535 · Cited by 30
Control of inflammatory heart disease by CD4+ T cells
Barin, J. G., & Čiháková, D. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12134 · Cited by 34
Severe Heterotopic Ossification in the Skeletal Muscle and Endothelial Cells Recruitment to Chondrogenesis Are Enhanced by Monocyte/Macrophage Depletion
Tirone, M., Giovenzana, A., Vallone, A., Zordan, P., Sormani, M., Nicolosi, P. A., Meneveri, R., Gigliotti, C. R., Spinelli, A. E., Bocciardi, R., et al. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01640 · Cited by 32
“A generalization of what is in vivo a broad and partially continuum set of differentiating populations suggests that activated MPs generate M1 (“classically activated”) and M2 (“alternatively activated”) cells (66).”
Background
Breast tumor cell TACE-shed MCSF promotes pro-angiogenic macrophages through NF-κB signaling
Rego, S. L., Helms, R. S., & Dréau, D. (2013) · Angiogenesis · doi:10.1007/s10456-013-9405-2 · Cited by 32
Innate Immune Cells in Breast Cancer – From Villains to Heroes?
Kees, T., & Egeblad, M. (2011) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-011-9224-2 · Cited by 31
“Cells of the innate immune system are specialists at the rapid elimination of pathogens [1] or infected cells, but are also important for the proper activation of the adaptive immune system, for tissue repair, and for physiological remodeling [ 2 , 3]. Macrophages are the cell type with the best characterized role in…”
Background
Resilience of dermis resident macrophages to inflammatory challenges
Lee, S. H., & Sacks, D. L. (2024) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01313-z · Cited by 34
Changes in energy metabolism and macrophage polarization: Potential mechanisms of arsenic-induced lung injury.
Wang, W.-J., Zheng, F., Lin, C.-H., & Zhang, A. (2020) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2020.110948 · Cited by 30
Leukemia inhibitory factor regulates the activation of inflammatory signals in macrophages and trophoblast cells.
Hamelin-Morrissette, J., Dallagi, A., Girouard, J., Ravelojaona, M., Oufqir, Y., Vaillancourt, C., Themsche, C. V., Carrier, C., & Reyes-Moreno, C. (2020) · Molecular Immunology · doi:10.1016/j.molimm.2020.01.021 · Cited by 30
Basic Concept of Microglia Biology and Neuroinflammation in Relation to Psychiatry
Mattei, D., & Notter, T. (2019) · Current topics in behavioral neurosciences · doi:10.1007/7854_2018_83 · Cited by 37
Immune Assisted Tissue Engineering via Incorporation of Macrophages in Cell-Laden Hydrogels Under Cytokine Stimulation
Barthès, J., Dollinger, C., Muller, C. B., Liivas, U., Dupret‐Bories, A., Knopf‐Marques, H., & Vrana, N. E. (2018) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2018.00108 · Cited by 35
Mammalian Target of Rapamycin Inhibition in Trypanosoma cruzi-Infected Macrophages Leads to an Intracellular Profile That Is Detrimental for Infection
Márquez, J. D. R., Ana, Y., Baigorrí, R. E., Stempin, C. C., & Cerbán, F. M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00313 · Cited by 42
Proangiogenic characteristics of activated macrophages from patients with age-related macular degeneration
Hagbi-Levi, S., Grunin, M. A., Jaouni, T., Tiosano, L., Rinsky, B., Elbaz-Hayoun, S., Peled, A., & Chowers, I. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.11.018 · Cited by 37
“Similar to IL-10, IL-6 also activates STAT3 which can result in enhanced angiogenesis (Izumi-Nagai et al., 2007).”
BackgroundMethodResultInfluential
Borrelia burgdorferi Arthritis–Associated Locus Bbaa1 Regulates Lyme Arthritis and K/B×N Serum Transfer Arthritis through Intrinsic Control of Type I IFN Production
Ma, Y., Bramwell, K. K. C., Lochhead, R. B., Paquette, J. K., Zachary, J. F., Weis, J. H., Teuscher, C., & Weis, J. J. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401746 · Cited by 29
Differences in PGE2 Production between Primary Human Monocytes and Differentiated Macrophages: Role of IL-1β and TRIF/IRF3
Endo, Y., Blinova, K., Romantseva, T., Golding, H., & Zaitseva, M. B. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098517 · Cited by 25
“Human elutriated monocytes and GM-CSF differentiated macrophages, which are considered to resemble inflammatory (M1) type of tissue macrophages [27], were used in the current study.”
Method
Truncated thioredoxin (Trx‐80) promotes pro‐inflammatory macrophages of the M1 phenotype and enhances atherosclerosis
Mahmood, D. F. D., Abderrazak, A., Couchie, D., Lunov, O., Diderot, V., Syrovets, T., Slimane, M.-N., Gosselet, F., Simmet, T., Rouis, M., et al. (2013) · Journal of Cellular Physiology · doi:10.1002/jcp.24319 · Cited by 34
“Macrophages are highly plastic cells that enter target tissues and gain the phenotypic and functional attributes of their tissue of residence (Mantovani et al., 2005).”
Background
Maternal exposure to airborne particulate matter causes postnatal immunological dysfunction in mice offspring
Hong, X., Liu, C., Chen, X., Song, Y., Wang, Q., Wang, P., & Hu, D. X. (2013) · Toxicology · doi:10.1016/j.tox.2013.02.004 · Cited by 32
IL-27 promotes nitric oxide production induced by LPS through STAT1, NF-κB and MAPKs
Shimizu, M., Ogura, K., Mizoguchi, I., Chiba, Y., Higuchi, K., Ohtsuka, H., Mizuguchi, J., & Yoshimoto, T. (2012) · Immunobiology · doi:10.1016/j.imbio.2012.07.028 · Cited by 34
ASSOCIATION OF TUMOR NECROSIS FACTOR α, INTERLEUKIN 6, AND INTERLEUKIN 10 PROMOTER POLYMORPHISM WITH PROLIFERATIVE DIABETIC RETINOPATHY IN TYPE 2 DIABETIC SUBJECTS
Paine, S. K., Sen, A., Choudhuri, S., Mondal, L. K., Chowdhury, I. H., Basu, A., Mukherjee, A., & Bhattacharya, B. (2011) · Retina · doi:10.1097/iae.0b013e31822f55f3 · Cited by 47
“It is alternatively stimulated by the influence of IL-4, IL-10, and IL-13 through TH2-associated effector functions and act as proangiogenic phenotype.(11) This alternatively activated macrophage or M2 macrophage produces low level of TNF-a and IL-6 with high level of IL-10.”
Background
Role of Polymorphonuclear Neutrophils on Infectious Complications Stemming from Enterococcus faecalis Oral Infection in Thermally Injured Mice
Tsuda, Y., Shigematsu, K., Kobayashi, M., Herndon, D. N., & Suzuki, F. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.6.4133 · Cited by 26
“M with abilities to produce IL-12/CCL3, to kill bacteria/tumor cells, and to induce Th1 cells are specifically designated as M1M (31, 36).”
Background
Cell-selective proteomics segregates pancreatic cancer subtypes by extracellular proteins in tumors and circulation
Swietlik, J. J., Bärthel, S., Falcomatà, C., Fink, D., Sinha, A., Cheng, J., Ebner, S., Landgraf, P., Dieterich, D. C., Daub, H., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38171-8 · Cited by 38
“…extremes on a spectrum of macrophage states — with M1 being associated with interferon and Toll-like receptor signals and ef ﬁ cient production of effector molecules and in ﬂ ammatory cytokines,andM2macrophageswiththeresolutionofin ﬂ ammationorT H 2 response-driven physiological reponses 52,53 .”
ROS inhibition increases KDM6A-mediated NOX2 transcription and promotes macrophages oxidative stress and M1 polarization
Zhao, Y., Wang, L., Liu, M., Du, A., Qiu, M., Shu, H., Li, L., Kong, X., & Sun, W. Y. (2023) · Cell Stress and Chaperones · doi:10.1007/s12192-023-01347-8 · Cited by 29
“Macrophages can also be induced to differentiate into M2 macrophages in the presence of interleukin 4 (IL-4), interleukin 13 (IL-13), or vitamin D3, and M2 macrophages tend to produce a large amount of interleukin 10 (IL-10) (Mantovani et al. 2005).”
Background
Exosomes: Carriers of Pro-Fibrotic Signals and Therapeutic Targets in Fibrosis
Li, M., Jiang, M., Meng, J., & Tao, L. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191209161443 · Cited by 38
Changes of peripheral TGF-β1 depend on monocytes-derived macrophages in Huntington disease
Pardo, A. D., Alberti, S., Maglione, V., Amico, E., Cortes, E. P., Elifani, F., Battaglia, G., Busceti, C. L., Nicoletti, F., Vonsattel, J., et al. (2013) · Molecular Brain · doi:10.1186/1756-6606-6-55 · Cited by 31
“Based on their activation state, macrophages can be divided into two polarized phenotypes known as M1, or “classical activated” and M2 or “alternative activated” macrophages [25,33].”
Background
Impaired antigen presentation and potent phagocytic activity identifying tumor-tolerant human monocytes
Schanoski, A. S., Jurado, T., Córdoba, R., Siliceo, M., del Fresno, C., Goméz-Piña, V., Toledano, V., Vallejo‐Cremades, M. T., Alfonso-Iñiguez, S., Carballo-Palos, A., et al. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.05.124 · Cited by 26
Herbal compound cepharanthine attenuates inflammatory arthritis by blocking macrophage M1 polarization
Lu, C., Cheng, R., Zhang, Q., Hu, Y., Pu, Y., Wen, J., Zhong, Y., Tang, Z., Wu, L., Wei, S., et al. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.111175 · Cited by 26
Porcine Macrophage Markers and Populations: An Update
Álvarez, B., Revilla, C., Poderoso, T., Ezquerra, Á., & Domínguez, J. (2023) · Cells · doi:10.3390/cells12162103 · Cited by 35
Role of Indole-3-Acetic Acid in NAFLD Amelioration After Sleeve Gastrectomy
Wang, Y., Wang, G., Bai, J., Zhao, N., Wang, Q., Zhou, R., Li, G., Hu, C., Li, X., Tao, K., et al. (2021) · Obesity Surgery · doi:10.1007/s11695-021-05321-0 · Cited by 27
“Macrophages are mainly divided into two phenotypes, namely classic activated macrophages (M1), which mainly produce inflammatory factors, and activated macrophages (M2), which mainly produce antiinflammatory factors [13, 14].”
Background

Authors: Mantovani, Sica, & Locati, M.
Affiliations: University of Milan (IT)
Corresponding author: Mantovani,, Alberto
ORCID: Mantovani,, Alberto
Sica,, Antonio
Locati, Massimo
Venue: Immunity
Publisher: Elsevier BV
Published: 2005-10
Volume: 23
Issue: 4
Pages: 344-346
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2005.10.001
OpenAlex: W1986736465
Cited by: 1,259
References: 0
Citations by year: 2026: 41 · 2025: 60 · 2024: 58 · 2023: 54 · 2022: 70 · 2021: 65 · 2020: 68 · 2019: 58 · 2018: 57 · 2017: 70 · 2016: 67 · 2015: 64 · 2014: 85 · 2013: 89 · 2012: 80
FWCI: 9.96
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2846 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Funders: Ministero dell’Istruzione, dell’Università e della Ricerca
Associazione Italiana per la Ricerca sul Cancro
European Commission
Ministero della Salute
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Keywords: macrophage polarization, M1 macrophages, M2 macrophages, mononuclear phagocytes, macrophage plasticity
MeSH terms: Cell Differentiation, Macrophages

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Macrophage Polarization Comes of Age

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