Metabolic programming of macrophage functions and pathogens control

Koo, Sue Jie; Garg, Nisha

doi:10.1016/j.redox.2019.101198

Cited by 83 publications

(73 citation statements)

References 141 publications

(165 reference statements)

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“…25,26 Besides, ATP produced by glucose metabolism can meet energy demands for many cellular activities, such as enzyme reaction, and electron transfer. 27 However, cellular metabolism not only provides the source of energy but also involves the inflammatory response. 28 For example, the glucose transporter 1 (GLUT1) which plays a key role in glucose uptake and glycolysis, can regulate the secretion of pro-inflammatory cytokines within macrophages.…”

Section: Introductionmentioning

confidence: 99%

Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO2 Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy

Chen¹,

Guan²,

Ren³

et al. 2020

IJN

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Introduction: The bone regeneration of endosseous implanted biomaterials is often impaired by the host immune response, especially macrophage-related inflammation which plays an important role in the bone healing process. Thus, it is a promising strategy to design an osteo-immunomodulatory biomaterial to take advantage of the macrophage-related immune response and improve the osseointegration performance of the implant. Methods: In this study, we developed an antibacterial silver nanoparticle-loaded TiO 2 nanotubes (Ag@TiO 2-NTs) using an electrochemical anodization method to make the surface modification and investigated the influences of Ag@TiO 2-NTs on the macrophage polarization, osteo-immune microenvironment as well as its potential molecular mechanisms in vitro and in vivo. Results: The results showed that Ag@TiO 2-NTs with controlled releasing of ultra-low-dose Ag + ions had the excellent ability to induce the macrophage polarization towards the M2 phenotype and create a suitable osteo-immune microenvironment in vitro, via inhibiting PI3K/Akt, suppressing the downstream effector GLUT1, and activating autophagy. Moreover, Ag@TiO 2-NTs surface could improve bone formation, suppress inflammation, and promote osteo-immune microenvironment compared to the TiO 2-NTs and polished Ti surfaces in vivo. These findings suggested that Ag@TiO 2-NTs with controlled releasing of ultra-low-dose Ag + ions could not only inhibit the inflammation process but also promote the bone healing by inducing healing-associated M2 polarization. Discussion: Using this surface modification strategy to modulate the macrophage-related immune response, rather than prevent the host response, maybe a promising strategy for implant surgeries in the future.

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Section: Introductionmentioning

confidence: 99%

Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO2 Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy

Chen¹,

Guan²,

Ren³

et al. 2020

IJN

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“…Although ONOO − has a short life, it is the most powerful cytotoxic effector produced by macrophages for parasite killing (Alvarez et al, 2011). Yet, it must be mentioned that the proinflammatory cytokines and the oxidative and nitrosative stress are capable of controlling, but not preventing the dissemination of virulent parasite strains from macrophages (reviewed in Lopez et al, 2018;Koo and Garg, 2019). This is, in part, attributed to the ability of the virulent isolates of T. cruzi to orchestrate their antioxidant system and allow sub-par and delayed activation of oxidative/nitrosative burst in the host immune cells (Piacenza et al, 2009b;Zago et al, 2016).…”

Section: Exposure To Oxidative and Nitrosative Stress In Immune Cellsmentioning

confidence: 99%

Redox Balance Keepers and Possible Cell Functions Managed by Redox Homeostasis in Trypanosoma cruzi

Mesías

Garg

Zago

2019

Front. Cell. Infect. Microbiol.

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The toxicity of oxygen and nitrogen reactive species appears to be merely the tip of the iceberg in the world of redox homeostasis. Now, oxidative stress can be seen as a two-sided process; at high concentrations, it causes damage to biomolecules, and thus, trypanosomes have evolved a strong antioxidant defense system to cope with these stressors. At low concentrations, oxidants are essential for cell signaling, and in fact, the oxidants/antioxidants balance may be able to trigger different cell fates. In this comprehensive review, we discuss the current knowledge of the oxidant environment experienced by T. cruzi along the different phases of its life cycle, and the molecular tools exploited by this pathogen to deal with oxidative stress, for better or worse. Further, we discuss the possible redox-regulated processes that could be governed by this oxidative context. Most of the current research has addressed the importance of the trypanosomes' antioxidant network based on its detox activity of harmful species; however, new efforts are necessary to highlight other functions of this network and the mechanisms underlying the fine regulation of the defense machinery, as this represents a master key to hinder crucial pathogen functions. Understanding the relevance of this balance keeper program in parasite biology will give us new perspectives to delineate improved treatment strategies.

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“…Macrophage metabolism is currently recognized as a key regulatory axis of macrophage activation and inflammatory responses . Different lines of evidence have shown that macrophage metabolic rewiring in response to microenvironment stimuli is tightly coupled to these cells ability to orchestrate inflammation and carry out their effector functions , . Accordingly, the metabolism of macrophages has been reported to sensitively respond to exposure to various types of nanoparticles, such as titanium dioxide, silica, poly(lactic‐co‐glycolic acid) and silk nanoparticles , .…”

Section: Introductionmentioning

confidence: 99%

Macrophage Metabolomics Reveals Differential Metabolic Responses to Subtoxic Levels of Silver Nanoparticles and Ionic Silver

et al. 2020

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This study employed NMR metabolomics to characterize macrophage responses to subtoxic concentrations of silver nanoparticles (AgNPs ca. 30 nm) and ionic silver (Ag + ), with a view to further elucidate their immunomodulatory activity at the cell metabolism level. Exposure to AgNPs caused RAW 264.7 macrophages to decrease intracellular glucose utilization, possibly due to interference with glycolytic enzymes, and to reprogram the TCA cycle towards anaplerotic fueling and production of anti-inflammatory metabolites (e.g. itaconate and creatine). Moreover, AgNPs-exposed cells were able to control the levels [a] Dr. 1867of reactive oxygen/nitrogen species (ROS/RNS), likely through upregulation of glutathione synthesis. On the other hand, macrophages exposed to Ag + at equivalent subtoxic concentrations showed reduced metabolic activity, lower ability to counterbalance ROS/RNS and alterations in membrane-related lipids. Overall, the metabolomics approach hereby employed provided novel insights into the differential effects of AgNPs and Ag + , which help explain the lower toxic potential of nanosilver than silver ions.ter. Moreover, since the release of silver ions from AgNPs has been highlighted as a main driver of AgNPs toxicity, [23] the metabolic effects of ionic silver (administered as AgNO 3 ), at inhibi-Joana Carrola graduated in Chemistry from the University of Porto, and obtained her PhD in Nanosciences and Nanotechnology, in 2017, from the University of Aveiro. Her PhD research focused on silver nanoparticles metabolism in mammalian cells. She is an expert in metabolomics, with interests in the study of drugs and nanomaterials metabolism.Verónica Bastos obtained her PhD in Biology studying nanotoxicity in in vitro cell cultures at the University of Aveiro, 2016. She is currently a Researcher in a project studying upconversion nanoparticles for multimodal therapy of melanoma at CESAM, Biology department of University of Aveiro. Her main research interests are related to nanotoxicity, nanobiomedicine and cancer therapy, ecotoxicology and human health. Ana Luísa Daniel-da-Silva graduated in Chemical Engineering by Instituto Superior Técnico (Lisbon, Portugal) in 2000 and obtained her PhD degree in Materials Science from the University of Alicante (Spain) in 2005. Since 2009 she is researcher at CICECO-Portugal. Her research focuses on the development of functional nanoparticles and nanocomposites for applications in nanomedicine, bionanotechnology and water remediation. and a member of CICECO-Aveiro Institute of Materials. Her main research interests are: 1) NMR metabolomics of biological systems (biofluids, intact tissues, tissue/material systems, cell cultures) subjected to disease, therapeutics, toxicological or environmental stresses for identification of novel biomarkers; 2) Metabolomic testing of novel biomaterials with applications in biodegradable implants, drug delivery or localized cell recognition; 3) Development of spectroscopy-based methods for food quality control.Conceição Santos is a Full Profes...

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Metabolic programming of macrophage functions and pathogens control

Cited by 83 publications

References 141 publications

<p>Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO<sub>2</sub> Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy</p>

<p>Improved Immunoregulation of Ultra-Low-Dose Silver Nanoparticle-Loaded TiO<sub>2</sub> Nanotubes via M2 Macrophage Polarization by Regulating GLUT1 and Autophagy</p>

Redox Balance Keepers and Possible Cell Functions Managed by Redox Homeostasis in Trypanosoma cruzi

Macrophage Metabolomics Reveals Differential Metabolic Responses to Subtoxic Levels of Silver Nanoparticles and Ionic Silver

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