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Disease Associated Macrophages: Old and New Standpoints
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Disease Associated Macrophages: Old and New Standpoints

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

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 11663

Special Issue Editors

Prof. Dr. Alessandra Castegna

E-Mail Website
Guest Editor
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, 70125 Bari, Italy
Interests: cell biology; neuroscience; Alzheimer's disease; biochemistry; biotechnology; oxidative stress; neurodegeneration; proteomics; proteins; antioxidants; immunometabolism; TAM; macrophage; glutamine; glutamine synthetase
Dr. Ionica Masgras

E-Mail Website
Guest Editor
Department of Biomedical Sciences-DSB, University of Padova, 35131 Padova, Italy
Interests: cancer metabolism; mitochondria
Prof. Dr. Massimiliano Mazzone

E-Mail Website
Guest Editor
Laboratory of Tumor Inflammation and Angiogenesis, Department of Oncology, KU Leuven, 3000 Leuven, Belgium
Interests: cancer; cancer metabolism
Dr. Carlos Sanchez-Martin

E-Mail Website
Guest Editor
Department of Biomedical Sciences-DSB, University of Padova, 35131 Padova, Italy
Interests: TRAP1; mitochondrial chaperone; cell metabolism

Special Issue Information

Dear Colleagues, 

Macrophages are innate immunocytes and have exceptionally diverse functions that include killing pathogens, tissue homeostasis, and wound healing. Research in the cancer field clearly indicates that tumor-associated macrophages (TAMs) as key components of the tumor microenvironment (TME), in which they interact with tumor cells and other key cellular components to promote tumor progression and metastasis. To delay or impede tumor growth, TAMs in the TME are increasingly being explored as a potential therapeutic target for which novel strategies need to be developed. From recent studies, novel scenarios are emerging, including the co-existence of different phenotypes of macrophages within the tumor, with pro- and anti-tumoral functions, and the role of macrophagic populations of different origins, each with specific peculiarities with respect to the TME biology. The mesmerizing variety of phenotypes is not merely specific to cancer but even more emphasized in virtually all diseases, ranging from cardiovascular diseases to obesity, chronic inflammations and infections, and muscle degeneration.

This issue invites experts to contribute original research reports as well as review articles that describe studies on macrophages in the context of cancer or other diseases.

Potential topics include, but are not limited to, the following themes:

  • Biology of the TME, with emphasis on TAM or other immune cells that infiltrate the TME;
  • A cluster of TAM phenotypes pre- and post-therapies (such as immune checkpoint blockade) and the extent of conservation across patients and species;
  • Description of new findings related to interactions of tumor cells with the TME;
  • Therapy concepts aiming at targeting macrophages to inhibit tumor growth;
  • Development of novel drug and novel carrier systems for macrophage targeting;
  • Novel methods related to tissue macrophage isolation and analysis;
  • Macrophage biology in the context of pathologies other than cancer: cardiovascular diseases, obesity, chronic inflammations and infections, and muscle degeneration.

Prof. Dr. Alessandra Castegna
Dr. Ionica Masgras
Prof. Dr. Massimiliano Mazzone
Dr. Carlos Sanchez-Martin
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • macrophages
  • tumor-associated macrophages (TAMs)
  • tumor microenvironment (TME)
  • immune cells

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Published Papers (4 papers)

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Research

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18 pages, 2863 KiB  
Article
Functional Crosstalk between PCSK9 Internalization and Pro-Inflammatory Activation in Human Macrophages: Role of Reactive Oxygen Species Release
by Rafael I. Jaén, Adrián Povo-Retana, César Rosales-Mendoza, Patricia Capillas-Herrero, Sergio Sánchez-García, Paloma Martín-Sanz, Marina Mojena, Patricia Prieto and Lisardo Boscá
Int. J. Mol. Sci. 2022, 23(16), 9114; https://doi.org/10.3390/ijms23169114 - 14 Aug 2022
Cited by 7 | Viewed by 2170
Abstract
Atherosclerosis is a cardiovascular disease caused mainly by dyslipidemia and is characterized by the formation of an atheroma plaque and chronic inflammation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease that induces the degradation of the LDL receptor (LDLR), which contributes to [...] Read more.
Atherosclerosis is a cardiovascular disease caused mainly by dyslipidemia and is characterized by the formation of an atheroma plaque and chronic inflammation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease that induces the degradation of the LDL receptor (LDLR), which contributes to increased levels of LDL cholesterol and the progress of atherosclerosis. Given that macrophages are relevant components of the lipidic and inflammatory environment of atherosclerosis, we studied the effects of PCSK9 treatment on human macrophages. Our data show that human macrophages do not express PCSK9 but rapidly incorporate the circulating protein through the LDLR and also activate the pro-inflammatory TLR4 pathway. Both LDLR and TLR4 are internalized after incubation of macrophages with exogenous PCSK9. PCSK9 uptake increases the production of reactive oxygen species and reduces the expression of genes involved in lipid metabolism and cholesterol efflux, while enhancing the production of pro-inflammatory cytokines through a TLR4-dependent mechanism. Under these conditions, the viability of macrophages is compromised, leading to increased cell death. These results provide novel insights into the role of PCSK9 in the crosstalk of lipids and cholesterol metabolism through the LDLR and on the pro-inflammatory activation of macrophages through TLR4 signaling. These pathways are relevant in the outcome of atherosclerosis and highlight the relevance of PCSK9 as a therapeutic target for the treatment of cardiovascular diseases. Full article
(This article belongs to the Special Issue Disease Associated Macrophages: Old and New Standpoints)
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Review

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16 pages, 1140 KiB  
Review
The Mac Is Back: The Role of Macrophages in Human Healthy and Complicated Pregnancies
by Juliette Krop, Xuezi Tian, Marie-Louise van der Hoorn and Michael Eikmans
Int. J. Mol. Sci. 2023, 24(6), 5300; https://doi.org/10.3390/ijms24065300 - 10 Mar 2023
Cited by 3 | Viewed by 3295
Abstract
Pregnancy is a fascinating immunological paradox: the semi-allogeneic fetus generally grows without any complications. In the placenta, fetal trophoblast cells come into contact with maternal immune cells. Inaccurate or inadequate adaptations of the maternal immune system could lead to problems with the functioning [...] Read more.
Pregnancy is a fascinating immunological paradox: the semi-allogeneic fetus generally grows without any complications. In the placenta, fetal trophoblast cells come into contact with maternal immune cells. Inaccurate or inadequate adaptations of the maternal immune system could lead to problems with the functioning of the placenta. Macrophages are important for tissue homeostasis, cleanup, and the repair of damaged tissues. This is crucial for a rapidly developing organ such as the placenta. The consensus on macrophages at the maternal-fetal interface in pregnancy is that a major proportion have an anti-inflammatory, M2-like phenotype, that expresses scavenger receptors and is involved in tissue remodeling and the dampening of the immune reactions. Recent multidimensional analyses have contributed to a more detailed outlook on macrophages. The new view is that this lineage represents a highly diverse phenotype and is more prevalent than previously thought. Spatial-temporal in situ analyses during gestation have identified unique interactions of macrophages both with trophoblasts and with T cells at different trimesters of pregnancy. Here, we elaborate on the role of macrophages during early human pregnancy and at later gestation. Their possible effect is reviewed in the context of HLA incompatibility between mother and fetus, first in naturally conceived pregnancies, but foremost in pregnancies after oocyte donation. The potential functional consequences of macrophages for pregnancy-related immune reactions and the outcome in patients with recurrent pregnancy loss are also discussed. Full article
(This article belongs to the Special Issue Disease Associated Macrophages: Old and New Standpoints)
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13 pages, 320 KiB  
Review
Macrophage Biology in Human Granulomatous Skin Inflammation
by Henning Klapproth, Manuel Huerta Arana and Mario Fabri
Int. J. Mol. Sci. 2023, 24(5), 4624; https://doi.org/10.3390/ijms24054624 - 27 Feb 2023
Cited by 2 | Viewed by 2024
Abstract
Cutaneous granulomatoses represent a heterogeneous group of diseases, which are defined by macrophage infiltration in the skin. Skin granuloma can be formed in the context of infectious and non-infectious conditions. Recent technological advances have deepened our understanding of the pathophysiology of granulomatous skin [...] Read more.
Cutaneous granulomatoses represent a heterogeneous group of diseases, which are defined by macrophage infiltration in the skin. Skin granuloma can be formed in the context of infectious and non-infectious conditions. Recent technological advances have deepened our understanding of the pathophysiology of granulomatous skin inflammation, and they provide novel insights into human tissue macrophage biology at the site of ongoing disease. Here, we discuss findings on macrophage immune function and metabolism derived from three prototypic cutaneous granulomatoses: granuloma annulare, sarcoidosis, and leprosy. Full article
(This article belongs to the Special Issue Disease Associated Macrophages: Old and New Standpoints)
18 pages, 5882 KiB  
Review
Reprogramming Metabolism of Macrophages as a Target for Kidney Dysfunction Treatment in Autoimmune Diseases
by Feng Tian, Hui Chen, Jianmin Zhang and Wei He
Int. J. Mol. Sci. 2022, 23(14), 8024; https://doi.org/10.3390/ijms23148024 - 21 Jul 2022
Cited by 4 | Viewed by 3341
Abstract
Chronic kidney disease (CKD), as one of the main complications of many autoimmune diseases, is difficult to cure, which places a huge burden on patients’ health and the economy and poses a great threat to human health. At present, the mainstream view is [...] Read more.
Chronic kidney disease (CKD), as one of the main complications of many autoimmune diseases, is difficult to cure, which places a huge burden on patients’ health and the economy and poses a great threat to human health. At present, the mainstream view is that autoimmune diseases are a series of diseases and complications caused by immune cell dysfunction leading to the attack of an organism’s tissues by its immune cells. The kidney is the organ most seriously affected by autoimmune diseases as it has a very close relationship with immune cells. With the development of an in-depth understanding of cell metabolism in recent years, an increasing number of scientists have discovered the metabolic changes in immune cells in the process of disease development, and we have a clearer understanding of the characteristics of the metabolic changes in immune cells. This suggests that the regulation of immune cell metabolism provides a new direction for the treatment and prevention of kidney damage caused by autoimmune diseases. Macrophages are important immune cells and are a double-edged sword in the repair process of kidney injury. Although they can repair damaged kidney tissue, over-repair will also lead to the loss of renal structural reconstruction function. In this review, from the perspective of metabolism, the metabolic characteristics of macrophages in the process of renal injury induced by autoimmune diseases are described, and the metabolites that can regulate the function of macrophages are summarized. We believe that treating macrophage metabolism as a target can provide new ideas for the treatment of the renal injury caused by autoimmune diseases. Full article
(This article belongs to the Special Issue Disease Associated Macrophages: Old and New Standpoints)
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