Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

Journal of Immunology Research, Jan 2018

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.

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Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders? Luca Parisi,1 Elisabetta Gini,2 Denisa Baci,3 Marco Tremolati,1 Matteo Fanuli,1 Barbara Bassani,2,3 Giampietro Farronato,1 Antonino Bruno,3 and Lorenzo Mortara2 1Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy 2Immunology and General Pathology Laboratory, Department of Biotechnology and Life Sciences, University of Insubria, Varese, Italy 3Scientific and Technologic Park, IRCCS MultiMedica, Milan, Italy Correspondence should be addressed to Luca Parisi; [email protected] and Barbara Bassani; [email protected] Received 23 July 2017; Revised 1 November 2017; Accepted 15 November 2017; Published 14 January 2018 Academic Editor: Kebin Hu Copyright © 2018 Luca Parisi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. 1. Introduction Macrophages belong to the mononuclear phagocyte system (MPS), a family of professional phagocytes that includes monocyte and dendritic cells (DCs). Over the past few decades, classification of the cells within the MPS system has generated considerable controversy given the different, often confusing, nomenclature to identify macrophages in different physio/pathological conditions as a consequence of their plasticity, resulting in very different phenotype/functions. The first open debate arises already in the definition of macrophage cell of origin. The classic scenario of the MPS stated that monocytes recruited from the periphery, under the influence of specific tissue-local growth factors, developed into macrophages. According to this scenario, macrophages derive from hematopoietic progenitors of bone marrow that differentiate under the influence of specific growth factors within the hosting tissues [1]. These cells primarily enter the blood as monocytes and further infiltrate tissues as macrophages, where they adapt to the local microenvironment to play out specific functions, such Kupffer cells in the liver, microglial cells in the brain [2], and mesangial cells in the kidney [3]. This view has been completely reconsidered over the last decade, and the ontogeny of macrophages has been totally rewritten, based on genetic approaches of cell fate mapping. New evidence demonstrated that macrophages can originate from embryonic precursor cells that colonized developing tissues before birth (foetal tissue macrophages) and that tissue-resident macrophages have self-maintaining abilities in the adulthood. Murine models allow the definition of three main sources for tissue-resident macrophages: (i) the yolk sac in the embryo as a source for progenitor cells by primitive hematopoiesis; (ii) the foetal liver, where the hematopoiesis takes places, shifting form the yolk sac, and (iii) the bone marrow that becomes the elicit hematopoietic centre in late embryos and adult organisms [4–6]. Another intriguing scenario, concerning the origin and persistence of macrophages, has been proposed by Gomez et al. [7]. The model proposed that resident macrophages, developing in the embryo independently of the hematopoietic stem cell (HSC) compartment [2, 8–11], still persist in adults and can coexist with the so termed “passenger” leucocytes that include monocytes and DCs, which originated from bone marrow HS (...truncated)


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Luca Parisi, Elisabetta Gini, Denisa Baci, Marco Tremolati, Matteo Fanuli, Barbara Bassani, Giampietro Farronato, Antonino Bruno, Lorenzo Mortara. Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?, Journal of Immunology Research, 2018, 2018, DOI: 10.1155/2018/8917804