Classical Dichotomy of Macrophages and Alternative Activation Models Proposed with Technological Progress

Abstract

Macrophages are important immune cells that participate in the regulation of inflammation in implant dentistry, and their activation/polarization state is considered to be the basis for their functions. The classic dichotomy activation model is commonly accepted, however, due to the discovery of macrophage heterogeneity and more functional and iconic exploration at different technologies; some studies have discovered the shortcomings of the dichotomy model and have put forward the concept of alternative activation models through the application of advanced technologies such as cytometry by time-of-flight (CyTOF), single-cell RNA-seq (scRNA-seq), and hyperspectral image (HSI). These alternative models have great potential to help macrophages divide phenotypes and functional genes.

Dynamics of tumor-associated macrophages in a quantitative systems pharmacology model of immunotherapy in triple-negative breast cancer

“…Macrophage polarization is an estimate of macrophage activation at a given time point, which is a plastic process and plays diverse roles in nonresolving inflammation like cancer ( Murray, 2017 ). Here, we adopted the classical dichotomy model for macrophages, which categorizes them into two subtypes: M1-and M2-like macrophages ( Wei et al., 2021 ). At the beginning of tumor development, monocytes are recruited first by CCL2 into the tumor where they differentiate to pro-inflammatory M1-like macrophages ( Yang et al., 2014 ).…”

From dichotomy to diversity: deciphering the multifaceted roles of tumor-associated macrophages in cancer progression and therapy

“…While useful as a conceptual framework, this dichotomous model is now recognized as an oversimplification due to the significant diversity in cell morphology, function, and cell surface marker expression in macrophages, suggesting that macrophage activation is a continuum in vivo 8,9 . TAMs display a diverse range of phenotypes in vivo that do not fit neatly into the M1/M2 categories 10 .…”

Potential effects of biomaterials on macrophage function and their signalling pathways

“…The classical macrophage dichotomy activation model, which can be viewed as a linear scale, categorises macrophages as M1 and M2 subtypes in vitro based on the type of stimulation, surface molecules, secreted cytokines profiles and functional features. 16 However, several studies have demonstrated that this model has shortcomings and cannot represent the entire macrophage activation process. Owing to the complex and diverse stimuli present in the microenvironment in vivo , as well as stimuli interactions, macrophages exhibit phenotypic heterogeneity and functional plasticity.…”