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The Journal of Allergy and Clinical... Aug 2023The pervasive role of the innate immune system is established by interferons. Emerging research shows an underappreciated ability of macrophages to regulate and... (Review)
Review
The pervasive role of the innate immune system is established by interferons. Emerging research shows an underappreciated ability of macrophages to regulate and propagate interferon responses in infectious and autoinflammatory disease states. In this review, we will discuss recent findings demonstrating the immunomodulating effects of macrophage interferon signaling. Apart from provoking cellular antimicrobial defenses, interferons augment the inflammatory activity of macrophages. These immunologic adaptations place the macrophage in the center of the interferon system and at the forefront of immunity. Consequently, macrophages are implicated in the pathogenesis of interferon-driven autoinflammatory disorders, such as SLE. In these disease states, the recognition of immunogenic ligands triggers macrophages to adopt an inflammatory phenotype through interferon signaling. This will amplify immune responses, eventually leading to autoinflammation. A better understanding of the macrophage's role in interferon signaling will support the future elucidation of novel targets amendable for clinical treatment.
Topics: Humans; Immunity, Innate; Macrophages; Inflammation; Interferons
PubMed: 37271317
DOI: 10.1016/j.jaci.2023.04.022 -
Current Opinion in Immunology Oct 2023Macrophages function as tissue-immune sentinels and mediate key antimicrobial responses against bacterial pathogens. Yet, they can also act as a cellular niche for... (Review)
Review
Macrophages function as tissue-immune sentinels and mediate key antimicrobial responses against bacterial pathogens. Yet, they can also act as a cellular niche for intracellular bacteria, such as Salmonella enterica, to persist in infected tissues. Macrophages exhibit heterogeneous activation or polarization, states that are linked to differential antibacterial responses and bacteria permissiveness. Remarkably, recent studies demonstrate that Salmonella and other intracellular bacteria inject virulence effectors into the cellular cytoplasm to skew the macrophage polarization state and reprogram these immune cells into a permissive niche. Here, we review mechanisms of macrophage reprogramming by Salmonella and highlight manipulation of macrophage polarization as a shared bacterial pathogenesis strategy. In addition, we discuss how the interplay of bacterial effector mechanisms, microenvironmental signals, and ontogeny may shape macrophage cell states and functions. Finally, we propose ideas of how further research will advance our understanding of macrophage functional diversity and immunobiology.
Topics: Humans; Macrophages; Bacteria; Virulence
PubMed: 37437470
DOI: 10.1016/j.coi.2023.102367 -
Frontiers in Immunology 2023
Topics: Gene Expression Regulation; Macrophages
PubMed: 38022640
DOI: 10.3389/fimmu.2023.1321064 -
Methods in Molecular Biology (Clifton,... 2024Macrophages were first described over a hundred years ago. Throughout the years, they were shown to be essential players in their tissue-specific environment, performing...
Macrophages were first described over a hundred years ago. Throughout the years, they were shown to be essential players in their tissue-specific environment, performing various functions during homeostatic and disease conditions. Recent reports shed more light on their ontogeny as long-lived, self-maintained cells with embryonic origin in most tissues. They populate the different tissues early during development, where they help to establish and maintain homeostasis. In this chapter, the history of macrophages is discussed. Furthermore, macrophage ontogeny and core functions in the different tissues are described.
Topics: Homeostasis; Macrophages
PubMed: 37639112
DOI: 10.1007/978-1-0716-3437-0_1 -
International Immunopharmacology Oct 2023Uniquely positioned as sentinel cells constantly exposed to the environment, pulmonary macrophages are vital for the maintenance of the lung lining. These cells are... (Review)
Review
Uniquely positioned as sentinel cells constantly exposed to the environment, pulmonary macrophages are vital for the maintenance of the lung lining. These cells are responsible for the clearance of xenobiotics, pathogen detection and clearance, and homeostatic functions such as surfactant recycling. Among the spectrum of phenotypes that may be expressed by macrophages in the lung, the pulmonary lipid-laden phenotype is less commonly studied in comparison to its circulatory counterpart, the atherosclerotic lesion-associated foam cell, or the acutely activated inflammatory macrophage. Herein, we propose that lipid-laden macrophage formation in the lung is governed by lipid acquisition, storage, metabolism, and export processes. The cellular balance of these four processes is critical to the maintenance of homeostasis and the prevention of aberrant signaling that may contribute to lung pathologies. This review aims to examine mechanisms and signaling pathways that are involved in lipid-laden macrophage formation and the potential consequences of this phenotype in the lung.
Topics: Macrophages; Macrophages, Alveolar; Foam Cells; Lung; Lipids
PubMed: 37595492
DOI: 10.1016/j.intimp.2023.110719 -
Nature Communications Nov 2023The transcriptional and phenotypic characteristics that define alveolar monocyte and macrophage subsets in acute hypoxemic respiratory failure (AHRF) are poorly...
The transcriptional and phenotypic characteristics that define alveolar monocyte and macrophage subsets in acute hypoxemic respiratory failure (AHRF) are poorly understood. Here, we apply CITE-seq (single-cell RNA-sequencing and cell-surface protein quantification) to bronchoalveolar lavage and blood specimens longitudinally collected from participants with AHRF to identify alveolar myeloid subsets, and then validate their identity in an external cohort using flow cytometry. We identify alveolar myeloid subsets with transcriptional profiles that differ from other lung diseases as well as several subsets with similar transcriptional profiles as reported in healthy participants (Metallothionein) or patients with COVID-19 (CD163/LGMN). We use information from CITE-seq to determine cell-surface proteins that distinguish transcriptional subsets (CD14, CD163, CD123, CD71, CD48, CD86 and CD44). In the external cohort, we find a higher proportion of CD163/LGMN alveolar macrophages are associated with mortality in AHRF. We report a parsimonious set of cell-surface proteins that distinguish alveolar myeloid subsets using scalable approaches that can be applied to clinical cohorts.
Topics: Humans; Macrophages, Alveolar; Macrophages; Monocytes; Lung Diseases; Respiratory Insufficiency
PubMed: 37978185
DOI: 10.1038/s41467-023-43223-0 -
Biomedicine & Pharmacotherapy =... Sep 2023Chronic wounds and scar formation are widespread due to limited suitable remedies. The macrophage is a crucial regulator in wound healing, controlling the onset and... (Review)
Review
Chronic wounds and scar formation are widespread due to limited suitable remedies. The macrophage is a crucial regulator in wound healing, controlling the onset and termination of inflammation and regulating other processes related to wound healing. The current breakthroughs in developing new medications and drug delivery methods have enabled the accurate targeting of macrophages in oncology and rheumatic disease therapies through clinical trials. These successes have cleared the way to utilize drugs targeting macrophages in various disorders. This review thus summarizes macrophage involvement in normal and pathologic wound healing. It further details the targets available for macrophage intervention and therapeutic strategies for targeting the behavior of macrophages in tissue repair and regeneration.
Topics: Humans; Wound Healing; Cicatrix; Macrophages; Drug Delivery Systems
PubMed: 37517288
DOI: 10.1016/j.biopha.2023.115199 -
Molecular Biology Reports Nov 2023Macrophages play a crucial role in regulating wound healing, as they undergo a transition from the proinflammatory M1 phenotype to the proliferative M2 phenotype,... (Review)
Review
Macrophages play a crucial role in regulating wound healing, as they undergo a transition from the proinflammatory M1 phenotype to the proliferative M2 phenotype, ultimately contributing to a favorable outcome. However, in hyperglycemic and hyper-reactive oxygen species environments, the polarization of macrophages becomes dysregulated, hindering the transition from the inflammatory to proliferative phase and consequently delaying the wound healing process. Consequently, regulating macrophage polarization is often regarded as a potential target for the treatment of diabetic wounds. The role of macrophages in wound healing and the changes in macrophages in diabetic conditions were discussed in this review. After that, we provide a discussion of recent therapeutic strategies for diabetic wounds that utilize macrophage polarization. Furthermore, this review also provides a comprehensive summary of the efficacious treatment strategies aimed at enhancing diabetic wound healing through the regulation of macrophage polarization. By encompassing a thorough understanding of the fundamental principles and their practical implementation, the advancement of treatment strategies for diabetic wounds can be further facilitated.
Topics: Animals; Diabetes Mellitus, Experimental; Wound Healing; Macrophages; Phenotype; Physiological Phenomena
PubMed: 37688679
DOI: 10.1007/s11033-023-08782-x -
Frontiers in Immunology 2023Excessive renal fibrosis is a common pathology in progressive chronic kidney diseases. Inflammatory injury and aberrant repair processes contribute to the development of...
Excessive renal fibrosis is a common pathology in progressive chronic kidney diseases. Inflammatory injury and aberrant repair processes contribute to the development of kidney fibrosis. Myeloid cells, particularly monocytes/macrophages, play a crucial role in kidney fibrosis by releasing their proinflammatory cytokines and extracellular matrix components such as collagen and fibronectin into the microenvironment of the injured kidney. Numerous signaling pathways have been identified in relation to these activities. However, the involvement of metabolic pathways in myeloid cell functions during the development of renal fibrosis remains understudied. In our study, we initially reanalyzed single-cell RNA sequencing data of renal myeloid cells from Dr. Denby's group and observed an increased gene expression in glycolytic pathway in myeloid cells that are critical for renal inflammation and fibrosis. To investigate the role of myeloid glycolysis in renal fibrosis, we utilized a model of unilateral ureteral obstruction in mice deficient of , an activator of glycolysis, in myeloid cells and their wild type littermates ( ). We observed a significant reduction in fibrosis in the obstructive kidneys of mice compared to mice. This was accompanied by a substantial decrease in macrophage infiltration, as well as a decrease of M1 and M2 macrophages and a suppression of macrophage to obtain myofibroblast phenotype in the obstructive kidneys of mice. Mechanistic studies indicate that glycolytic metabolites stabilize HIF1α, leading to alterations in macrophage phenotype that contribute to renal fibrosis. In conclusion, our study implicates that targeting myeloid glycolysis represents a novel approach to inhibit renal fibrosis.
Topics: Animals; Mice; Fibrosis; Glycolysis; Kidney; Kidney Diseases; Macrophages; Phosphofructokinase-2
PubMed: 38035106
DOI: 10.3389/fimmu.2023.1259434 -
Drug Resistance Updates : Reviews and... Mar 2024Macrophages are important components of the immune system. Mature macrophages can be recruited to tumor microenvironment that affect tumor cell proliferation, invasion... (Review)
Review
Macrophages are important components of the immune system. Mature macrophages can be recruited to tumor microenvironment that affect tumor cell proliferation, invasion and metastasis, extracellular matrix remodeling, immune suppression, as well as chemotherapy resistance. Classically activated type I macrophages (M1) exhibited marked tumor killing and phagocytosis. Therefore, using macrophages for adoptive cell therapy has attracted attention and become one of the most effective strategies for cancer treatment. Through cytokines and/or chemokines, macrophage can inhibit myeloid cells recruitment, and activate anti-tumor and immune killing functions. Applying macrophages for anti-tumor delivery is one of the most promising approaches for cancer therapy. This review article introduces the role of macrophages in tumor development and drug resistance, and the possible clinical application of targeting macrophages for overcoming drug resistance and enhancing cancer therapeutics, as well as its challenges.
Topics: Humans; Tumor-Associated Macrophages; Macrophages; Neoplasms; Cytokines; Tumor Microenvironment
PubMed: 38198845
DOI: 10.1016/j.drup.2023.101041