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Special Issue "Macrophages in Inflammation"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 June 2018).

Special Issue Editors

Guest Editor
Prof. Dr. Andrij Holian

University of Montana Missoula, Department of Biomedical and Pharmaceutical Sciences, Missoula, USA
Website | E-Mail
Interests: nanoparticles; particulate matter; asbestos; silica; alveolar macrophages; innate immunity; NLRP3 inflammasome; macrophage receptors; lysosomes
Guest Editor
Dr. Christopher Migliaccio

Center for Environmental Health Sciences, University of Montana; Missoula, MT, USA
Website | E-Mail
Interests: macrophage phenotypes; inflammation; wildfire smoke; nanomaterials; silica
Guest Editor
Prof. Dr. Mary Gulumian

Toxicology and Biochemistry Section NIOH, P O Box 4788 Johannesburg 2000, Reader Professor: School of Pathology, University of the Witwatersrand; South Africa
Website | E-Mail
Interests: nanomaterials; silica; asbestos; nanotoxicology; in vitro methodologies; risk assessment; occupational toxicology; macrophages; lysosomes

Special Issue Information

Dear Colleagues,

Macrophages are involved in both innate and adaptive immune responses to regulate both acute and chronic inflammation. Macrophages have been recognized as key regulators of many diseases. They are plastic and respond to their microenvironments with amazing adaptability and function. Therefore, based on their key roles in regulating inflammation, it is important to bring together the most current information to identify gaps of knowledge that need to be filled in understanding how their many functions are regulated in order to assist and guide future research to treat human diseases. This Special Issue will include studies that describe their responses to endogenous and exogenous triggers, regulation of phentypes and responses, key steps in regulating their functions, their roles in acute and chronic inflammation, therapeutic approaches to regulate their functions.

Prof. Dr. Andrij Holian
Dr. Christopher  Migliaccio
Prof. Dr. Mary Gulumian
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Acute inflammation
  • Chronic inflammation
  • Macrophage phenotypes
  • Macrophage function in diseases
  • Therapeutic approaches
  • Lysosome permeabilization and inflammasomes in macrophage function

Related Special Issue

Published Papers (18 papers)

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Research

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Open AccessArticle
PPARγ Expression Is Diminished in Macrophages of Recurrent Miscarriage Placentas
Int. J. Mol. Sci. 2018, 19(7), 1872; https://doi.org/10.3390/ijms19071872
Received: 23 May 2018 / Revised: 18 June 2018 / Accepted: 19 June 2018 / Published: 26 June 2018
Cited by 4 | PDF Full-text (5662 KB) | HTML Full-text | XML Full-text
Abstract
PPARγ belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPARγ is also a main factor for macrophage polarization. The aim of this study [...] Read more.
PPARγ belongs to the group of nuclear receptors which is expressed in the trophoblast and together with other factors is responsible for the maintenance of pregnancy. Apart from that PPARγ is also a main factor for macrophage polarization. The aim of this study was to investigate the combined expression pattern and frequency of PPARγ under physiological circumstances and in spontaneous and recurrent miscarriages in the trophoblast and in maternal macrophages of the decidua. Human placental tissues of the first trimester (15 physiologic pregnancies, 15 spontaneous abortion and 16 recurrent miscarriage placentas) were analyzed for expression of the nuclear receptor PPARγ. Expression changes were evaluated by immunohistochemistry and real time PCR (RT-PCR) in trophoblast and in maternal macrophages of the decidua. Maternal macrophages were identified by double immunofluorescence using cluster of differentiation 68 (CD68) as marker for macrophages and further characterized regarding their M1/M2 polarization status. The intermediate villous trophoblast revealed a significantly lower PPARγ expression in spontaneous and recurrent abortion. Maternal macrophages express PPARγ. Their number is significantly enhanced in the decidua of spontaneous miscarriages whereas in recurrent miscarriages maternal macrophages seem to express PPARγ only in very few cases. PPARγ is associated with an M2 polarization state that is common for decidual macrophages. The lack of PPARγ in recurrent miscarriage decidual macrophages seems to be associated with a specific inflammatory response against the fetus. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessArticle
Macrophage Populations in Visceral Adipose Tissue from Pregnant Women: Potential Role of Obesity in Maternal Inflammation
Int. J. Mol. Sci. 2018, 19(4), 1074; https://doi.org/10.3390/ijms19041074
Received: 15 February 2018 / Revised: 22 March 2018 / Accepted: 26 March 2018 / Published: 4 April 2018
Cited by 1 | PDF Full-text (31594 KB) | HTML Full-text | XML Full-text
Abstract
Obesity is associated with inflammatory changes and accumulation and phenotype polarization of adipose tissue macrophages (ATMs). Obese pregnant women have alterations in adipose tissue composition, but a detailed description of macrophage population is not available. In this study, we characterized macrophage populations in [...] Read more.
Obesity is associated with inflammatory changes and accumulation and phenotype polarization of adipose tissue macrophages (ATMs). Obese pregnant women have alterations in adipose tissue composition, but a detailed description of macrophage population is not available. In this study, we characterized macrophage populations in visceral adipose tissue (VAT) from pregnant women with normal, overweight, and obese pregestational weight. Immunophenotyping of macrophages from VAT biopsies was performed by flow cytometry using CD45 and CD14 as markers of hematopoietic and monocyte linage, respectively, while HLA-DR, CD11c, CD163, and CD206 were used as pro- and anti-inflammatory markers. Adipocyte number and size were evaluated by light microscopy. The results show that pregnant women that were overweight and obese during the pregestational period had adipocyte hypertrophy. Two different macrophage populations in VAT were identified: recruited macrophages (CD45+CD14+), and a novel population lacking CD45, which was considered to be a resident macrophages subset (CD45CD14+). The number of resident HLADRlow/− macrophages showed a negative correlation with body mass index (BMI). Both resident and recruited macrophages from obese women expressed higher CD206 levels. CD11c expression was higher in resident HLA-DR+ macrophages from obese women. A strong correlation between CD206 and CD11c markers and BMI was observed. Our findings show that being overweight and obese in the pregestational period is associated with adipocyte hypertrophy and specific ATMs populations in VAT. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessArticle
Distinct Properties of Human M-CSF and GM-CSF Monocyte-Derived Macrophages to Simulate Pathological Lung Conditions In Vitro: Application to Systemic and Inflammatory Disorders with Pulmonary Involvement
Int. J. Mol. Sci. 2018, 19(3), 894; https://doi.org/10.3390/ijms19030894
Received: 8 March 2018 / Revised: 15 March 2018 / Accepted: 15 March 2018 / Published: 17 March 2018
Cited by 3 | PDF Full-text (1777 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Macrophages play a central role in the pathogenesis of inflammatory and fibrotic lung diseases. However, alveolar macrophages (AM) are poorly available in humans to perform in vitro studies due to a limited access to broncho-alveolar lavage (BAL). In this study, to identify the [...] Read more.
Macrophages play a central role in the pathogenesis of inflammatory and fibrotic lung diseases. However, alveolar macrophages (AM) are poorly available in humans to perform in vitro studies due to a limited access to broncho-alveolar lavage (BAL). In this study, to identify the best alternative in vitro model for human AM, we compared the phenotype of AM obtained from BAL of patients suffering from three lung diseases (lung cancers, sarcoidosis and Systemic Sclerosis (SSc)-associated interstitial lung disease) to human blood monocyte-derived macrophages (MDMs) differentiated with M-CSF or GM-CSF. The expression of eight membrane markers was evaluated by flow cytometry. Globally, AM phenotype was closer to GM-CSF MDMs. However, the expression levels of CD163, CD169, CD204, CD64 and CD36 were significantly higher in SSc-ILD than in lung cancers. Considering the expression of CD204 and CD36, the phenotype of SSc-AM was closer to MDMs, from healthy donors or SSc patients, differentiated by M-CSF rather than GM-CSF. The comparative secretion of IL-6 by SSc-MDMs and SSc-AM is concordant with these phenotypic considerations. Altogether, these results support the M-CSF MDM model as a relevant in vitro alternative to simulate AM in fibrotic disorders such as SSc. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessArticle
The Effects of Varying Degree of MWCNT Carboxylation on Bioactivity in Various In Vivo and In Vitro Exposure Models
Int. J. Mol. Sci. 2018, 19(2), 354; https://doi.org/10.3390/ijms19020354
Received: 13 December 2017 / Revised: 16 January 2018 / Accepted: 23 January 2018 / Published: 25 January 2018
Cited by 4 | PDF Full-text (5820 KB) | HTML Full-text | XML Full-text
Abstract
Functionalization has been shown to alter toxicity of multi-walled carbon nanotube (MWCNT) in several studies. This study varied the degree of functionalization (viz., amount of MWCNT surface carboxylation) to define the relationship between the extent of carboxylation and effects in a variety of [...] Read more.
Functionalization has been shown to alter toxicity of multi-walled carbon nanotube (MWCNT) in several studies. This study varied the degree of functionalization (viz., amount of MWCNT surface carboxylation) to define the relationship between the extent of carboxylation and effects in a variety of in vitro cell models and short-term ex vivo/in vivo particle exposures. Studies with vitamin D3 plus phorbol ester transformed THP-1 macrophages demonstrated that functionalization, regardless of amount, corresponded with profoundly decreased NLRP3 inflammasome activation. However, all MWCNT variants were slightly toxic in this model. Alternatively, studies with A549 epithelial cells showed some varied effects. For example, IL-33 and TNF-α release were related to varying amounts of functionalization. For in vivo particle exposures, autophagy of alveolar macrophages, measured using green fluorescent protein (GFP)- fused-LC3 transgenic mice, increased for all MWCNT tested three days after exposure, but, by Day 7, autophagy was clearly dependent on the amount of carboxylation. The instilled source MWCNT continued to produce cellular injury in alveolar macrophages over seven days. In contrast, the more functionalized MWCNT initially showed similar effects, but reduced over time. Dark-field imaging showed the more functionalized MWCNTs were distributed more uniformly throughout the lung and not isolated to macrophages. Taken together, the results indicated that in vitro and in vivo bioactivity of MWCNT decreased with increased carboxylation. Functionalization by carboxylation eliminated the bioactive potential of the MWCNT in the exposure models tested. The observation that maximally functionalized MWCNT distribute more freely throughout the lung with the absence of cellular damage, and extended deposition, may establish a practical use for these particles as a safer alternative for unmodified MWCNT. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessArticle
Time Course of the Phenotype of Blood and Bone Marrow Monocytes and Macrophages in the Lung after Cigarette Smoke Exposure In Vivo
Int. J. Mol. Sci. 2017, 18(9), 1940; https://doi.org/10.3390/ijms18091940
Received: 25 July 2017 / Revised: 30 August 2017 / Accepted: 4 September 2017 / Published: 9 September 2017
Cited by 5 | PDF Full-text (14273 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Alveolar macrophages play a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Monocytes are recruited from blood during inflammation and then mature into alveolar macrophages. The aim of this study was to investigate the effect of cigarette smoke (CS) at [...] Read more.
Alveolar macrophages play a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Monocytes are recruited from blood during inflammation and then mature into alveolar macrophages. The aim of this study was to investigate the effect of cigarette smoke (CS) at different times in lung macrophages and monocytes from blood and bone marrow in mice. Male mice (C57BL/6, n = 45) were divided into groups: control, CS 5 days, CS 14 days and CS 30 days. Five days’ CS exposure induced a pronounced influx of neutrophils and macrophages in the lung associated with increased levels of keratinocyte chemoattractant (KC), tumor necrosis factor-α (TNF-α), nitric oxide (NO) and matrix metalloproteinase (MMP)-12. After 14 days of CS exposure, neutrophil recruitment and cytokine production were greatly reduced. Moreover, chronic CS exposure led to increased recruitment of macrophages (with high expression of CD206), transforming growth factor-β (TGF-β) production as well as no detection of TNF-α, interleukin (IL)-6 and KC. CS can also change the monocyte phenotype in the blood and bone marrow, with an increase in Ly6Clow cells. These results show for the first time that CS can change not only macrophage polarization but also monocyte. These results suggest that continued recruitment of Ly6Clow monocytes may help the distinct renewing macrophage M2 population required for COPD progression. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Review

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Open AccessReview
Innate Immunity Cells and the Neurovascular Unit
Int. J. Mol. Sci. 2018, 19(12), 3856; https://doi.org/10.3390/ijms19123856
Received: 21 September 2018 / Revised: 26 November 2018 / Accepted: 30 November 2018 / Published: 3 December 2018
Cited by 4 | PDF Full-text (2570 KB) | HTML Full-text | XML Full-text
Abstract
Recent studies have clarified many still unknown aspects related to innate immunity and the blood-brain barrier relationship. They have also confirmed the close links between effector immune system cells, such as granulocytes, macrophages, microglia, natural killer cells and mast cells, and barrier functionality. [...] Read more.
Recent studies have clarified many still unknown aspects related to innate immunity and the blood-brain barrier relationship. They have also confirmed the close links between effector immune system cells, such as granulocytes, macrophages, microglia, natural killer cells and mast cells, and barrier functionality. The latter, in turn, is able to influence not only the entry of the cells of the immune system into the nervous tissue, but also their own activation. Interestingly, these two components and their interactions play a role of great importance not only in infectious diseases, but in almost all the pathologies of the central nervous system. In this paper, we review the main aspects in the field of vascular diseases (cerebral ischemia), of primitive and secondary neoplasms of Central Nervous System CNS, of CNS infectious diseases, of most common neurodegenerative diseases, in epilepsy and in demyelinating diseases (multiple sclerosis). Neuroinflammation phenomena are constantly present in all diseases; in every different pathological state, a variety of innate immunity cells responds to specific stimuli, differentiating their action, which can influence the blood-brain barrier permeability. This, in turn, undergoes anatomical and functional modifications, allowing the stabilization or the progression of the pathological processes. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
Monocytes and Macrophages as Viral Targets and Reservoirs
Int. J. Mol. Sci. 2018, 19(9), 2821; https://doi.org/10.3390/ijms19092821
Received: 26 June 2018 / Revised: 10 September 2018 / Accepted: 14 September 2018 / Published: 18 September 2018
Cited by 3 | PDF Full-text (851 KB) | HTML Full-text | XML Full-text
Abstract
Viruses manipulate cell biology to utilize monocytes/macrophages as vessels for dissemination, long-term persistence within tissues and virus replication. Viruses enter cells through endocytosis, phagocytosis, macropinocytosis or membrane fusion. These processes play important roles in the mechanisms contributing to the pathogenesis of these agents [...] Read more.
Viruses manipulate cell biology to utilize monocytes/macrophages as vessels for dissemination, long-term persistence within tissues and virus replication. Viruses enter cells through endocytosis, phagocytosis, macropinocytosis or membrane fusion. These processes play important roles in the mechanisms contributing to the pathogenesis of these agents and in establishing viral genome persistence and latency. Upon viral infection, monocytes respond with an elevated expression of proinflammatory signalling molecules and antiviral responses, as is shown in the case of the influenza, Chikungunya, human herpes and Zika viruses. Human immunodeficiency virus initiates acute inflammation on site during the early stages of infection but there is a shift of M1 to M2 at the later stages of infection. Cytomegalovirus creates a balance between pro- and anti-inflammatory processes by inducing a specific phenotype within the M1/M2 continuum. Despite facilitating inflammation, infected macrophages generally display abolished apoptosis and restricted cytopathic effect, which sustains the virus production. The majority of viruses discussed in this review employ monocytes/macrophages as a repository but certain viruses use these cells for productive replication. This review focuses on viral adaptations to enter monocytes/macrophages, immune escape, reprogramming of infected cells and the response of the host cells. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
Chemopreventive Effects of Phytochemicals and Medicines on M1/M2 Polarized Macrophage Role in Inflammation-Related Diseases
Int. J. Mol. Sci. 2018, 19(8), 2208; https://doi.org/10.3390/ijms19082208
Received: 26 June 2018 / Revised: 16 July 2018 / Accepted: 23 July 2018 / Published: 28 July 2018
Cited by 9 | PDF Full-text (2281 KB) | HTML Full-text | XML Full-text
Abstract
Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines [...] Read more.
Macrophages can polarize into two different states (M1 and M2), which play contrasting roles during pathogenesis or tissue damage. M1 polarized macrophages produce pro-inflammatory cytokines and mediators resulting in inflammation, while M2 macrophages have an anti-inflammatory effect. Secretion of appropriate cytokines and chemokines from macrophages can lead to the modification of the microenvironment for bridging innate and adaptive immune responses. Increasing evidence suggests that polarized macrophages are pivotal for disease progression, and the regulation of macrophage polarization may provide a new approach in therapeutic treatment of inflammation-related diseases, including cancer, obesity and metabolic diseases, fibrosis in organs, brain damage and neuron injuries, and colorectal disease. Polarized macrophages affect the microenvironment by secreting cytokines and chemokines while cytokines or mediators that are produced by resident cells or tissues may also influence macrophages behavior. The interplay of macrophages and other cells can affect disease progression, and therefore, understanding the activation of macrophages and the interaction between polarized macrophages and disease progression is imperative prior to taking therapeutic or preventive actions. Manipulation of macrophages can be an entry point for disease improvement, but the mechanism and potential must be understood. In this review, some advanced studies regarding the role of macrophages in different diseases, potential mechanisms involved, and intervention of drugs or phytochemicals, which are effective on macrophage polarization, will be discussed. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
Role of Human Macrophage Polarization in Inflammation during Infectious Diseases
Int. J. Mol. Sci. 2018, 19(6), 1801; https://doi.org/10.3390/ijms19061801
Received: 21 March 2018 / Revised: 4 May 2018 / Accepted: 6 May 2018 / Published: 19 June 2018
Cited by 19 | PDF Full-text (666 KB) | HTML Full-text | XML Full-text
Abstract
Experimental models have often been at the origin of immunological paradigms such as the M1/M2 dichotomy following macrophage polarization. However, this clear dichotomy in animal models is not as obvious in humans, and the separating line between M1-like and M2-like macrophages is rather [...] Read more.
Experimental models have often been at the origin of immunological paradigms such as the M1/M2 dichotomy following macrophage polarization. However, this clear dichotomy in animal models is not as obvious in humans, and the separating line between M1-like and M2-like macrophages is rather represented by a continuum, where boundaries are still unclear. Indeed, human infectious diseases, are characterized by either a back and forth or often a mixed profile between the pro-inflammatory microenvironment (dominated by interleukin (IL)-1β, IL-6, IL-12, IL-23 and Tumor Necrosis Factor (TNF)-α cytokines) and tissue injury driven by classically activated macrophages (M1-like) and wound healing driven by alternatively activated macrophages (M2-like) in an anti-inflammatory environment (dominated by IL-10, Transforming growth factor (TGF)-β, chemokine ligand (CCL)1, CCL2, CCL17, CCL18, and CCL22). This review brews the complexity of the situation during infectious diseases by stressing on this continuum between M1-like and M2-like extremes. We first discuss the basic biology of macrophage polarization, function, and role in the inflammatory process and its resolution. Secondly, we discuss the relevance of the macrophage polarization continuum during infectious and neglected diseases, and the possibility to interfere with such activation states as a promising therapeutic strategy in the treatment of such diseases. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
Macrophage MicroRNAs as Therapeutic Targets for Atherosclerosis, Metabolic Syndrome, and Cancer
Int. J. Mol. Sci. 2018, 19(6), 1756; https://doi.org/10.3390/ijms19061756
Received: 2 May 2018 / Revised: 5 June 2018 / Accepted: 8 June 2018 / Published: 13 June 2018
Cited by 4 | PDF Full-text (1132 KB) | HTML Full-text | XML Full-text
Abstract
Macrophages play a crucial role in the innate immune system and contribute to a broad spectrum of pathologies in chronic inflammatory diseases. MicroRNAs (miRNAs) have been demonstrated to play important roles in macrophage functions by regulating macrophage polarization, lipid metabolism and so on. [...] Read more.
Macrophages play a crucial role in the innate immune system and contribute to a broad spectrum of pathologies in chronic inflammatory diseases. MicroRNAs (miRNAs) have been demonstrated to play important roles in macrophage functions by regulating macrophage polarization, lipid metabolism and so on. Thus, miRNAs represent promising diagnostic and therapeutic targets in immune disorders. In this review, we will summarize the role of miRNAs in atherosclerosis, metabolic syndrome, and cancer by modulating macrophage phenotypes, which has been supported by in vivo evidence. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
The Cholinergic Anti-Inflammatory Response and the Role of Macrophages in HIV-Induced Inflammation
Int. J. Mol. Sci. 2018, 19(5), 1473; https://doi.org/10.3390/ijms19051473
Received: 6 March 2018 / Revised: 11 April 2018 / Accepted: 29 April 2018 / Published: 16 May 2018
PDF Full-text (913 KB) | HTML Full-text | XML Full-text
Abstract
Macrophages are phagocytic immune cells that protect the body from foreign invaders and actively support the immune response by releasing anti- and proinflammatory cytokines. A seminal finding revolutionized the way macrophages are seen. The expression of the neuronal alpha7 nicotinic acetylcholine receptor (α7-nAChR) [...] Read more.
Macrophages are phagocytic immune cells that protect the body from foreign invaders and actively support the immune response by releasing anti- and proinflammatory cytokines. A seminal finding revolutionized the way macrophages are seen. The expression of the neuronal alpha7 nicotinic acetylcholine receptor (α7-nAChR) in macrophages led to the establishment of the cholinergic anti-inflammatory response (CAR) in which the activation of this receptor inactivates macrophage production of proinflammatory cytokines. This novel neuroimmune response soon began to emerge as a potential target to counteract inflammation during illness and infection states. Human immunodeficiency virus (HIV)-infected individuals suffer from chronic inflammation that persists even under antiretroviral therapy. Despite the CAR’s importance, few studies involving macrophages have been performed in the HIV field. Evidence demonstrates that monocyte-derived macrophages (MDMs) recovered from HIV-infected individuals are upregulated for α7-nAChR. Moreover, in vitro studies demonstrate that addition of an HIV viral constituent, gp120IIIB, to uninfected MDMs also upregulates the α7-nAChR. Importantly, contrary to what was expected, activation of upregulated α7-nAChRs in macrophages does not reduce inflammation, suggesting a CAR disruption. Although it is reasonable to consider this receptor as a pharmacological target, additional studies are necessary since its activity seems to differ from that observed in neurons. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
Role of Macrophages in Brain Tumor Growth and Progression
Int. J. Mol. Sci. 2018, 19(4), 1005; https://doi.org/10.3390/ijms19041005
Received: 3 February 2018 / Revised: 10 March 2018 / Accepted: 23 March 2018 / Published: 27 March 2018
Cited by 10 | PDF Full-text (3042 KB) | HTML Full-text | XML Full-text
Abstract
The role of macrophages in the growth and the progression of tumors has been extensively studied in recent years. A large body of data demonstrates that macrophage polarization plays an essential role in the growth and progression of brain tumors, such as gliomas, [...] Read more.
The role of macrophages in the growth and the progression of tumors has been extensively studied in recent years. A large body of data demonstrates that macrophage polarization plays an essential role in the growth and progression of brain tumors, such as gliomas, meningiomas, and medulloblastomas. The brain neoplasm cells have the ability to influence the polarization state of the tumor associated macrophages. In turn, innate immunity cells have a decisive role through regulation of the acquired immune response, but also through humoral cross-talking with cancer cells in the tumor microenvironment. Neoangiogenesis, which is an essential element in glial tumor progression, is even regulated by the tumor associated macrophages, whose activity is linked to other factors, such as hypoxia. In addition, macrophages play a decisive role in establishing the entry into the bloodstream of cancer cells. As is well known, the latter phenomenon is also present in brain tumors, even if they only rarely metastasize. Looking ahead in the future, we can imagine that characterizing the relationships between tumor and tumor associated macrophage, as well as the study of circulating tumor cells, could give us useful tools in prognostic evaluation and therapy. More generally, the study of innate immunity in brain tumors can boost the development of new forms of immunotherapy. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
The Role of Macrophages in Neuroinflammatory and Neurodegenerative Pathways of Alzheimer’s Disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis: Pathogenetic Cellular Effectors and Potential Therapeutic Targets
Int. J. Mol. Sci. 2018, 19(3), 831; https://doi.org/10.3390/ijms19030831
Received: 23 February 2018 / Revised: 9 March 2018 / Accepted: 12 March 2018 / Published: 13 March 2018
Cited by 12 | PDF Full-text (917 KB) | HTML Full-text | XML Full-text
Abstract
In physiological conditions, different types of macrophages can be found within the central nervous system (CNS), i.e., microglia, meningeal macrophages, and perivascular (blood-brain barrier) and choroid plexus (blood-cerebrospinal fluid barrier) macrophages. Microglia and tissue-resident macrophages, as well as blood-borne monocytes, have different origins, [...] Read more.
In physiological conditions, different types of macrophages can be found within the central nervous system (CNS), i.e., microglia, meningeal macrophages, and perivascular (blood-brain barrier) and choroid plexus (blood-cerebrospinal fluid barrier) macrophages. Microglia and tissue-resident macrophages, as well as blood-borne monocytes, have different origins, as the former derive from yolk sac erythromyeloid precursors and the latter from the fetal liver or bone marrow. Accordingly, specific phenotypic patterns characterize each population. These cells function to maintain homeostasis and are directly involved in the development and resolution of neuroinflammatory processes. Also, following inflammation, circulating monocytes can be recruited and enter the CNS, therefore contributing to brain pathology. These cell populations have now been identified as key players in CNS pathology, including autoimmune diseases, such as multiple sclerosis, and degenerative diseases, such as Amyotrophic Lateral Sclerosis and Alzheimer’s disease. Here, we review the evidence on the involvement of CNS macrophages in neuroinflammation and the advantages, pitfalls, and translational opportunities of pharmacological interventions targeting these heterogeneous cellular populations for the treatment of brain diseases. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
Lung Macrophage Phenotypes and Functional Responses: Role in the Pathogenesis of COPD
Int. J. Mol. Sci. 2018, 19(2), 582; https://doi.org/10.3390/ijms19020582
Received: 15 January 2018 / Revised: 7 February 2018 / Accepted: 10 February 2018 / Published: 15 February 2018
Cited by 5 | PDF Full-text (3400 KB) | HTML Full-text | XML Full-text
Abstract
Lung macrophages (LMs) are essential immune effector cells that are pivotal in both innate and adaptive immune responses to inhaled foreign matter. They either reside within the airways and lung tissues (from early life) or are derived from blood monocytes. Similar to macrophages [...] Read more.
Lung macrophages (LMs) are essential immune effector cells that are pivotal in both innate and adaptive immune responses to inhaled foreign matter. They either reside within the airways and lung tissues (from early life) or are derived from blood monocytes. Similar to macrophages in other organs and tissues, LMs have natural plasticity and can change phenotype and function depending largely on the microenvironment they reside in. Phenotype changes in lung tissue macrophages have been implicated in chronic inflammatory responses and disease progression of various chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). LMs have a wide variety of functional properties that include phagocytosis (inorganic particulate matter and organic particles, such as viruses/bacteria/fungi), the processing of phagocytosed material, and the production of signaling mediators. Functioning as janitors of the airways, they also play a key role in removing dead and dying cells, as well as cell debris (efferocytic functions). We herein review changes in LM phenotypes during chronic lung disease, focusing on COPD, as well as changes in their functional properties as a result of such shifts. Targeting molecular pathways involved in LM phenotypic shifts could potentially allow for future targeted therapeutic interventions in several diseases, such as COPD. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
Inflammatory Alteration of Human T Cells Exposed Continuously to Asbestos
Int. J. Mol. Sci. 2018, 19(2), 504; https://doi.org/10.3390/ijms19020504
Received: 4 January 2018 / Revised: 5 February 2018 / Accepted: 6 February 2018 / Published: 8 February 2018
Cited by 1 | PDF Full-text (866 KB) | HTML Full-text | XML Full-text
Abstract
Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous [...] Read more.
Asbestos is a known carcinogen and exposure can lead to lung cancer and malignant mesothelioma. To examine the effects of asbestos fibers on human immune cells, the human T cell leukemia/lymphoma virus (HTLV)-1 immortalized human T cell line MT-2 was employed. Following continuous exposure to asbestos fibers for more than eight months, MT-2 sublines showed acquisition of resistance to asbestos-induced apoptosis with decreased death signals and increased surviving signals. These sublines showed various characteristics that suggested a reduction in anti-tumor immunity. On the other hand, inflammatory changes such as expression of MMP7, CXCR5, CXCL13 and CD44 was found to be markedly higher in sublines continuously exposed to asbestos compared with original MT-2 cells. All of these molecules contribute to lung inflammation, T and B cell interactions and connections between mesothelial cells and T cells. Thus, further investigation focusing on these molecules may shed light on the role of chronic inflammation caused by asbestos exposure and the occurrence of malignant mesothelioma. Finally, regarding peripheral T cells from healthy donors (HD) and asbestos-exposed patients with pleural plaque (PP) or malignant pleural mesothelioma (MPM), following stimulation of CD4+ T cells, T cells from MPM patients showed reduced potential of interferon (IFN)-γ expression. Moreover, levels of interleukin (IL)-6, one of the most important cytokines in chronic inflammation, in cultured supernatants were higher in PP and MPM patients compared with HD. Overall, asbestos-induced chronic inflammation in the lung as well as the pleural cavity may facilitate the onset of asbestos-induced cancers due to alterations in the interactions among fibers, immune cells such as T and B cells and macrophages, and mesothelial and lung epithelial cells. Further investigations regarding chronic inflammation caused by asbestos fibers may assist in identifying molecular targets for preventive and therapeutic strategies related to the effects of asbestos exposure. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis
Int. J. Mol. Sci. 2018, 19(1), 92; https://doi.org/10.3390/ijms19010092
Received: 28 November 2017 / Revised: 19 December 2017 / Accepted: 27 December 2017 / Published: 29 December 2017
Cited by 10 | PDF Full-text (461 KB) | HTML Full-text | XML Full-text
Abstract
Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead [...] Read more.
Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions. Recent studies demonstrated that macrophages differentiate from hematopoietic stem cell-derived monocytes and embryonic yolk sac macrophages. The latter mainly give rise to tissue macrophages. Macrophages exist in all vertebrate tissues and have dual functions in host protection and tissue injury, which are maintained at a fine balance. Tissue macrophages have heterogeneous phenotypes in different tissue environments. In this review, we focused on the phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis for a better understanding of the role of tissue macrophages in several pathological conditions. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
IFN-β: A Contentious Player in Host–Pathogen Interaction in Tuberculosis
Int. J. Mol. Sci. 2017, 18(12), 2725; https://doi.org/10.3390/ijms18122725
Received: 14 November 2017 / Revised: 8 December 2017 / Accepted: 12 December 2017 / Published: 16 December 2017
Cited by 2 | PDF Full-text (1350 KB) | HTML Full-text | XML Full-text
Abstract
Tuberculosis (TB) is a major health threat to the human population worldwide. The etiology of the disease is Mycobacterium tuberculosis (Mtb), a highly successful intracellular pathogen. It has the ability to manipulate the host immune response and to make the intracellular environment suitable [...] Read more.
Tuberculosis (TB) is a major health threat to the human population worldwide. The etiology of the disease is Mycobacterium tuberculosis (Mtb), a highly successful intracellular pathogen. It has the ability to manipulate the host immune response and to make the intracellular environment suitable for its survival. Many studies have addressed the interactions between the bacteria and the host immune cells as involving many immune mediators and other cellular players. Interferon-β (IFN-β) signaling is crucial for inducing the host innate immune response and it is an important determinant in the fate of mycobacterial infection. The role of IFN-β in protection against viral infections is well established and has been studied for decades, but its role in mycobacterial infections remains much more complicated and debatable. The involvement of IFN-β in immune evasion mechanisms adopted by Mtb has been an important area of investigation in recent years. These advances have widened our understanding of the pro-bacterial role of IFN-β in host–pathogen interactions. This pro-bacterial activity of IFN-β appears to be correlated with its anti-inflammatory characteristics, primarily by antagonizing the production and function of interleukin 1β (IL-1β) and interleukin 18 (IL-18) through increased interleukin 10 (IL-10) production and by inhibiting the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome. Furthermore, it also fails to provoke a proper T helper 1 (Th1) response and reduces the expression of major histocompatibility complex II (MHC-II) and interferon-γ receptors (IFNGRs). Here we will review some studies to provide a paradigm for the induction, regulation, and role of IFN-β in mycobacterial infection. Indeed, recent studies suggest that IFN-β plays a role in Mtb survival in host cells and its downregulation may be a useful therapeutic strategy to control Mtb infection. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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Open AccessReview
Pharmacological Regulation of Neuropathic Pain Driven by Inflammatory Macrophages
Int. J. Mol. Sci. 2017, 18(11), 2296; https://doi.org/10.3390/ijms18112296
Received: 19 October 2017 / Revised: 27 October 2017 / Accepted: 31 October 2017 / Published: 1 November 2017
Cited by 8 | PDF Full-text (1349 KB) | HTML Full-text | XML Full-text
Abstract
Neuropathic pain can have a major effect on quality of life but current therapies are often inadequate. Growing evidence suggests that neuropathic pain induced by nerve damage is caused by chronic inflammation. Upon nerve injury, damaged cells secrete pro-inflammatory molecules that activate cells [...] Read more.
Neuropathic pain can have a major effect on quality of life but current therapies are often inadequate. Growing evidence suggests that neuropathic pain induced by nerve damage is caused by chronic inflammation. Upon nerve injury, damaged cells secrete pro-inflammatory molecules that activate cells in the surrounding tissue and recruit circulating leukocytes to the site of injury. Among these, the most abundant cell type is macrophages, which produce several key molecules involved in pain enhancement, including cytokines and chemokines. Given their central role in the regulation of peripheral sensitization, macrophage-derived cytokines and chemokines could be useful targets for the development of novel therapeutics. Inhibition of key pro-inflammatory cytokines and chemokines prevents neuroinflammation and neuropathic pain; moreover, recent studies have demonstrated the effectiveness of pharmacological inhibition of inflammatory (M1) macrophages. Nicotinic acetylcholine receptor ligands and T helper type 2 cytokines that reduce M1 macrophages are able to relieve neuropathic pain. Future translational studies in non-human primates will be crucial for determining the regulatory mechanisms underlying neuroinflammation-associated neuropathic pain. In turn, this knowledge will assist in the development of novel pharmacotherapies targeting macrophage-driven neuroinflammation for the treatment of intractable neuropathic pain. Full article
(This article belongs to the Special Issue Macrophages in Inflammation)
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