M1/M2 macrophages and their overlaps – myth or reality?

Strizova, Z., Benesova, I., Bartolini, R. , Novysedlak, R., Cecrdlova, E., Koumbas Foley, L. and Striz, I. (2023) M1/M2 macrophages and their overlaps – myth or reality? Clinical Science, 137, pp. 1067-1093. (doi: 10.1042/CS20220531) (PMID:37530555) (PMCID:PMC10407193)

Abstract

Macrophages represent heterogeneous cell population with important roles in defence mechanisms and in homoeostasis. Tissue macrophages from diverse anatomical locations adopt distinct activation states. M1 and M2 macrophages are two polarized forms of mononuclear phagocyte in vitro differentiation with distinct phenotypic patterns and functional properties, but in vivo, there is a wide range of different macrophage phenotypes in between depending on the microenvironment and natural signals they receive. In human infections, pathogens use different strategies to combat macrophages and these strategies include shaping the macrophage polarization towards one or another phenotype. Macrophages infiltrating the tumours can affect the patient’s prognosis. M2 macrophages have been shown to promote tumour growth, while M1 macrophages provide both tumour-promoting and anti-tumour properties. In autoimmune diseases, both prolonged M1 activation, as well as altered M2 function can contribute to their onset and activity. In human atherosclerotic lesions, macrophages expressing both M1 and M2 profiles have been detected as one of the potential factors affecting occurrence of cardiovascular diseases. In allergic inflammation, T2 cytokines drive macrophage polarization towards M2 profiles, which promote airway inflammation and remodelling. M1 macrophages in transplantations seem to contribute to acute rejection, while M2 macrophages promote the fibrosis of the graft. The view of pro-inflammatory M1 macrophages and M2 macrophages suppressing inflammation seems to be an oversimplification because these cells exploit very high level of plasticity and represent a large scale of different immunophenotypes with overlapping properties. In this respect, it would be more precise to describe macrophages as M1-like and M2-like.

• Item Type: Articles
• Additional Information: Research was supported by funding from the Charles University - project GA UK No. 94323; the Ministry of Health, Czech Republic - project AZV NU23J-08-00031, by MHCR - conceptual development of research organization (“Institute for Clinical and Experimental Medicine – IKEM, IN 00023001”), by a Wellcome Trust Investigator Award (217093/Z/19/Z) and a MRC Programme Grant (MR/V010972/1).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Koumbas Foley, Lily and Bartolini, Mr Robin
• Authors: Strizova, Z., Benesova, I., Bartolini, R., Novysedlak, R., Cecrdlova, E., Koumbas Foley, L., and Striz, I.
• College/School: College of Medical Veterinary and Life Sciences; College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Clinical Science
• Publisher: Portland Press
• ISSN: 0143-5221
• ISSN (Online): 1470-8736
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Clinical Science 137:1067–1093
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
306649		Defining chemokine receptor involvement in the myelomonocytic inflammatory response	Gerard Graham	Wellcome Trust (WELLCOTR)	217093/Z/19/Z	SII - Immunology & Infection
308056		Placental chemokine compartmentalisation by atypical chemokine receptors.	Gerard Graham	Medical Research Council (MRC)	MR/V010972/1	SII - Immunology & Infection