Current Concept and Update of the Macrophage Plasticity Concept: Intracellular Mechanisms of Reprogramming and M3 Macrophage "Switch" Phenotype.

Igor Malyshev,Yuri Malyshev

doi:10.1155/2015/341308

Abstract

Macrophages play a key role in immunity. In this review, we consider the traditional notion of macrophage plasticity, data that do not fit into existing concepts, and a hypothesis for existence of a new switch macrophage phenotype. Depending on the microenvironment, macrophages can reprogram their phenotype toward the proinflammatory M1 phenotype or toward the anti-inflammatory M2 phenotype. Macrophage reprogramming involves well-coordinated changes in activities of signalling and posttranslational mechanisms. Macrophage reprogramming is provided by JNK-, PI3K/Akt-, Notch-, JAK/STAT-, TGF-β-, TLR/NF-κB-, and hypoxia-dependent pathways. Posttranscriptional regulation is based on micro-mRNA. We have hypothesized that, in addition to the M1 and M2 phenotypes, an M3 switch phenotype exists. This switch phenotype responds to proinflammatory stimuli with reprogramming towards the anti-inflammatory M2 phenotype or, contrarily, it responds to anti-inflammatory stimuli with reprogramming towards the proinflammatory M1 phenotype. We have found signs of such a switch phenotype in lung diseases. Understanding the mechanisms of macrophage reprogramming will assist in the selection of new therapeutic targets for correction of impaired immunity.

Highlights

The immune system recognizes and eliminates pathogenic microbial products and tumor cells, preventing the progression of many diseases
The intracellular network of miRs possesses all the features of a regulatory mechanism of macrophage reprogramming, including both positive and negative feedbacks, and a specificity of action on the receptors and proteins participating in macrophage reprogramming
A few generalities can be made concerning the miR-dependent regulation of the phenotype of macrophages: (1) There is a certain specificity in the expression of miRs; miR-155, miR-21, miR-29b, miR-125, miR-9, miR-146a, and miR-147 are expressed in response to reprogramming factor- (RF-)M1, whereas miR-146b, miR-511, miR-187, miR378, miR-222, miR-27a, miR-125a-3p, and miR-125a5p are expressed in response to RF-M2

Summary

Introduction

The immune system recognizes and eliminates pathogenic microbial products and tumor cells, preventing the progression of many diseases. Macrophages are the sensor cells of the immune system They identify pathogenic cells with pattern recognition receptors (PRR), such as Toll-like receptors (TLR) [5], and water-soluble pattern recognition molecules (PRM), such as ficolins and collectins [6]. They play an important role in the neutralization of such microbes as Aspergillus fumigates and Pseudomonas aeruginosa. The efficacy of immune defence depends on the extent of macrophage plasticity, that is, on how quickly and adequately the cells can change their functional phenotype in response to the microenvironment and pathogenic microbes. We will consider published experimental data that do not conform to the current concept of macrophage plasticity. These data lead us to hypothesize a new macrophage phenotype, which we name the switch phenotype

Macrophage M1 And M2 Phenotypes

Paradoxical Plasticity of Macrophages

Conclusions

Findings

Conflict of Interests