Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

Abstract

Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1) or alternatively activated (M2). However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like) and/or builders (M2-like). We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

Punicalagin, a Pomegranate‐Derived Ellagitannin, Suppresses Obesity and Obesity‐Induced Inflammatory Responses Via the Nrf2/Keap1 Signaling Pathway

“…The ATM modulation correlated with the regulation of cytokines by PCG: mRNA expression of inflammatory cytokines, including IL‐1β, IL‐6, and TNF‐α, was decreased, but the expression of an anti‐inflammatory cytokine, IL‐10, was increased. As M1/M2 regulation has been associated with the complexities of metabolic diseases such as obesity and diabetes, these results indicate that PCG may have the potential to block progression of these diseases by regulation of the ATM phenotypes.…”

“…The polarization of ATMs is an important marker of inflammatory status in obesity . There are two distinct ATM phenotypes: M1 macrophages are classically activated and are associated with pro‐inflammatory cytokines and reactive oxygen species (ROS); the alternatively activated M2 macrophages are associated with anti‐inflammatory cytokines and are involved in the resolution of inflammatory processes . PCG differentially regulated these ATM phenotypes: the amount of CD11c, an M1 marker protein, was decreased after administration of PCG, but the amount of CD206, an M2 surface marker, was increased.…”

Differential transcriptional profiles identify microglial- and macrophage-specific gene markers expressed during virus-induced neuroinflammation

“…Different from microglia, macrophages are derived from monocytes, which originate from bone marrow hematopoietic stem cells (reviewed in [17]). Like microglia, macrophages possess high plasticity, adapting and changing phenotype depending on the surrounding environment, and they contribute to proinflammatory responses as well as healing responses [18,19].…”

“…Upon activation, macrophages can acquire distinct phenotypes such as the classically defined M1, or proinflammatory, and M2, or anti-inflammatory, polarization states. While M1 polarization correlates with the induction of inflammation through the secretion of proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, induction of the M2 phenotype results in secretion of anti-inflammatory mediators, favoring tissue repair and homeostasis [1,5,18,19]. It is important to mention that change in macrophage phenotype is a spectrum and not a binary state, implying that both states can be found simultaneously.…”

Monounsaturated Fatty Acids in a High‐Fat Diet and Niacin Protect from White Fat Dysfunction in the Metabolic Syndrome

“…Upon exceeding its expansion capacity by an enlargement in the size of adipocytes (hypertrophy), an increase in the number of adipocytes (hyperplasia) or both, WAT becomes dysfunctional and promotes the recruitment of immune cells, which ultimately leads to a low‐grade inflammatory state . Self‐sustained lipolysis orchestrates the accumulation of monocyte‐derived macrophages in the obese WAT, where they polarize or switch from an M2 anti‐inflammatory phenotype toward an M1 pro‐inflammatory phenotype . Such a pathological WAT remodeling particularly occurs with long‐lasting ingestion of Westernized, high‐fat diets (HFDs) rich in saturated fatty acids (SFAs) in both humans and murine models .…”