scholarly journals Exosome-Depleted Excretory-Secretory Products of the Fourth-Stage Larval Angiostrongylus cantonensis Promotes Alternative Activation of Macrophages Through Metabolic Reprogramming by the PI3K-Akt Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Shuo Wan ◽  
Xiaoqiang Sun ◽  
Wenyan Tang ◽  
Lifu Wang ◽  
Zhongdao Wu ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Angiostrongylus Cantonensis ◽  
Metabolic Reprogramming ◽  
Alternative Activation ◽  
Akt Pathway ◽  
Eosinophilic Meningitis ◽  
Fourth Stage ◽  
Mice Model ◽  
Secretory Products

Angiostrongylus cantonensis (AC), which parasitizes in the brain of the non-permissive host, such as mouse and human, is an etiologic agent of eosinophilic meningitis. Excretory-secretory (ES) products play an important role in the interaction between parasites and hosts’ immune responses. Inflammatory macrophages are responsible for eosinophilic meningitis induced by AC, and the soluble antigens of Angiostrongylus cantonensis fourth stage larva (AC L4), a mimic of dead AC L4, aggravate eosinophilic meningitis in AC-infected mice model via promoting alternative activation of macrophages. In this study, we investigated the key molecules in the ES products of AC L4 on macrophages and observed the relationship between metabolic reprogramming and the PI3K-Akt pathway. First, a co-culture system of macrophage and AC L4 was established to define the role of AC L4 ES products on macrophage polarization. Then, AC L4 exosome and exosome-depleted excretory-secretory products (exofree) were separated from AC L4 ES products using differential centrifugation, and their distinct roles on macrophage polarization were confirmed using qPCR and ELISA experiments. Moreover, AC L4 exofree induced alternative activation of macrophages, which is partially associated with metabolic reprogramming by the PI3K-Akt pathway. Next, lectin blot and deglycosylation assay were done, suggesting the key role of N-linked glycoproteins in exofree. Then, glycoproteomic analysis of exofree and RNA-seq analysis of exofree-treated macrophage were performed. Bi-layer PPI network analysis based on these results identified macrophage-related protein Hexa as a key molecule in inducing alternative activation of macrophages. Our results indicate a great value for research of helminth-derived immunoregulatory molecules, which might contribute to drug development for immune-related diseases.

scholarly journals Arachidonic Acid Metabolism Controls Macrophage Alternative Activation Through Regulating Oxidative Phosphorylation in PPARγ Dependent Manner

2021 ◽  
Vol 12 ◽  
Author(s):  
Miao Xu ◽  
Xiaohong Wang ◽  
Yongning Li ◽  
Xue Geng ◽  
Xudong Jia ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Oxidative Phosphorylation ◽  
Acid Metabolism ◽  
Macrophage Polarization ◽  
Arachidonic Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Alternative Activation ◽  
Dependent Manner ◽  
M2 Polarization

Macrophage polarization is mainly steered by metabolic reprogramming in the tissue microenvironment, thus leading to distinct outcomes of various diseases. However, the role of lipid metabolism in the regulation of macrophage alternative activation is incompletely understood. Using human THP-1 and mouse bone marrow derived macrophage polarization models, we revealed a pivotal role for arachidonic acid metabolism in determining the phenotype of M2 macrophages. We demonstrated that macrophage M2 polarization was inhibited by arachidonic acid, but inversely facilitated by its derived metabolite prostaglandin E2 (PGE2). Furthermore, PPARγ bridges these two seemingly unrelated processes via modulating oxidative phosphorylation (OXPHOS). Through inhibiting PPARγ, PGE2 enhanced OXPHOS, resulting in the alternative activation of macrophages, which was counterweighted by the activation of PPARγ. This connection between PGE2 biosynthesis and macrophage M2 polarization also existed in human and mouse esophageal squamous cell carcinoma. Our results highlight the critical role of arachidonic acid and metabolic PGE2 as immune regulators in modulating tissue homeostasis and pathological process.

scholarly journals Macrophage polarization in sarcoidosis

2021 ◽  
Vol 23 (1) ◽  
pp. 7-16
Author(s):  
I. E. Malysheva ◽  
E. L. Tikhonovich ◽  
E. K. Oleinik ◽  
L. V. Topchieva ◽  
O. V. Balan
Keyword(s):  
Macrophage Polarization ◽  
Adaptive Immune Response ◽  
Granulomatous Inflammation ◽  
Epithelioid Cell ◽  
Alternative Activation ◽  
Unknown Etiology ◽  
New Therapeutic Approaches ◽  
Systemic Inflammatory Disease ◽  
M2 Phenotype

Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the formation of epithelioid cell granulomas, multisystem lesions with a certain frequency of involvement of various organs, mainly the lungs (up to 90% of cases). Over the past decade, significant progress has been made in understanding the pathogenesis of sarcoidosis, the important role of immunological, genetic and environmental factors in the development of this pathology has been established. It is believed that the leading mechanism in the pathogenesis of sarcoidosis is the aberrant activation of the innate and adaptive immune response to unidentified antigen(s), which leads to the development of granulomatous inflammation and the formation of granulomas. However, despite the huge number of studies that has been carried out, the mechanisms and signaling pathways that control the development of the inflammatory process during the formation of granulomas and the progression of pathology have not been fully determined.This literature review examines the important role of various cytokines and T helper subpopulations in sarcoidosis. Particular attention is paid to the cells of innate immunity – macrophages in the pathogenesis of this disease. These cells play a key role in the formation of sarcoid granulomas and in the pathogenesis of sarcoidosis. The macrophage population is characterized by plasticity and functional heterogeneity. In response to various signals from the microenvironment, macrophages are able to acquire certain phenotypes. The review considers the issues of polarization of macrophages, changes in the phenotype of these cells to subpopulations M1 (M1 phenotype; classically activated; pro-inflammatory) and M2 (M2 phenotype; alternatively activated, anti-inflammatory). These two cell populations are characterized by the expression of different markers on their surface, which allow these cells to differentiate from each other. The analysis of literature data on the levels of key polarizing cytokines for macrophages and cells-producers of these cytokines that patients with sarcoidosis have, in acute and chronic course of the disease, was carried out.Important aspects of the alternative activation of macrophages of the M2 phenotype and their division into subtypes: M2a, M2b, M2c, M2d are noted. The features of various subtypes’ activation of macrophages in this granulomatosis and their importance in the development and progression of pathology are considered. Studying the role of macrophages’ phenotypes, understanding the mechanisms by which the phenotypes of these cells are activated and modulated in various microenvironmental conditions, can contribute to the development and implementation into clinical practice of new therapeutic approaches for the treatment of sarcoidosis and many other forms of pathologies.

scholarly journals Eosinophilic meningitis in New Caledonia: The role of Angiostrongylus cantonensis?

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254964
Author(s):  
Bénédicte Melot ◽  
Gauthier Delvallez ◽  
Ann-Claire Gourinat ◽  
Nicolas Molko ◽  
Cyrille Goarant ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Retrospective Study ◽  
New Caledonia ◽  
Angiostrongylus Cantonensis ◽  
Eosinophilic Meningitis ◽  
Rare Form ◽  
High Incidence ◽  
Target Prevention ◽  
Two Peaks

Introduction Eosinophilic meningitis is a rare form of meningitis with sequelae or death occurring in approximately 2–3% of cases. The most frequent etiological agent is the parasite Angiostrongylus cantonensis. The aim of this study was to characterize New Caledonian cases and to assess the extent to which of A. cantonensis was involved. Material and methods We performed a retrospective study of all cases of eosinophilic meningitis (EM) admitted to the Territorial Hospital of New Caledonia, from 2004 to 2019. We performed a descriptive and a multivariate analysis to identify association of variables with severe and fatal cases (or cases with sequelae). Conclusion Angiostrongyliasis was confirmed as being responsible for 17 of the 92 reported EM cases in New Caledonia from 2004 to 2019 with most being young adults and non-walking infants, and with two peaks of incidence one during the dry season and one during the rainy season. Considering the high incidence and regularity of cases, the potential reservoirs should be identified to target prevention campaigns.

scholarly journals Novel Role of Endogenous Catalase in Macrophage Polarization in Adipose Tissue

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Ye Seul Park ◽  
Md Jamal Uddin ◽  
Lingjuan Piao ◽  
Inah Hwang ◽  
Jung Hwa Lee ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Alternative Activation ◽  
Phenotypic Switch ◽  
Raw264.7 Macrophages ◽  
Adipose Tissue Macrophages

Macrophages are important components of adipose tissue inflammation, which results in metabolic diseases such as insulin resistance. Notably, obesity induces a proinflammatory phenotypic switch in adipose tissue macrophages, and oxidative stress facilitates this switch. Thus, we examined the role of endogenous catalase, a key regulator of oxidative stress, in the activity of adipose tissue macrophages in obese mice. Catalase knockout (CKO) exacerbated insulin resistance, amplified oxidative stress, and accelerated macrophage infiltration into epididymal white adipose tissue in mice on normal or high-fat diet. Interestingly, catalase deficiency also enhanced classical macrophage activation (M1) and inflammation but suppressed alternative activation (M2) regardless of diet. Similarly, pharmacological inhibition of catalase activity using 3-aminotriazole induced the same phenotypic switch and inflammatory response in RAW264.7 macrophages. Finally, the same phenotypic switch and inflammatory responses were observed in primary bone marrow-derived macrophages from CKO mice. Taken together, the data indicate that endogenous catalase regulates the polarization of adipose tissue macrophages and thereby inhibits inflammation and insulin resistance.

scholarly journals Arachidonic acid metabolism controls macrophage alternative activation through regulating oxidative phosphorylation in PPARG dependent manner

2020 ◽  
Author(s):  
Miao Xu ◽  
Xiaohong Wang ◽  
Xudong Jia ◽  
Yongning Li ◽  
Xue Geng ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Oxidative Phosphorylation ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Alternative Activation ◽  
M2 Macrophage ◽  
Dependent Manner ◽  
Macrophages Polarization

AbstractMacrophages polarization is mainly controlled by metabolic reprogramming in microenvironment, thus leading to distinct outcomes of various diseases. However, the role of lipid metabolism in the regulation of macrophage alternative activation is incompletely understood. Using human THP-1 and mouse bone marrow derived macrophages polarization models, we revealed a pivotal role for arachidonic acid metabolism in controlling the polarization of M1 and M2 macrophages. We demonstrated that M2 macrophage polarization was inhibited by arachidonic acid, but inversely facilitated by its derived metabolite prostaglandin E2 (PGE2). Furthermore, PPARG bridges these two unconnected processes via modulating oxidative phosphorylation. These results highlight the critical role of arachidonic acid metabolism as an immune regulator in modulating metabolic homeostasis and pathological process.

Protective Role of Mitophagy Associated Metabolic Reprogramming of Peripheral Macrophages During Tuberculosis

2020 ◽  
Author(s):  
Ranjeet Singh Mahla ◽  
Akhilesh Kumar ◽  
Helena Tutil ◽  
Sreevidhya Tarakkad Krishnaji ◽  
Bharathwaj Sathyamoorthy ◽  
...  
Keyword(s):  
Protective Role ◽  
Metabolic Reprogramming

scholarly journals Exosomes from human umbilical cord mesenchymal stem cells attenuate the inflammation of severe steroid-resistant asthma by reshaping macrophage polarization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bing Dong ◽  
Chao Wang ◽  
Jing Zhang ◽  
Jinrong Zhang ◽  
Yinuo Gu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Quantitative Proteomics ◽  
Macrophage Polarization ◽  
Human Umbilical Cord ◽  
Raw 264.7 ◽  
Steroid Resistant ◽  
Central Protein

Abstract Background Severe, steroid-resistant asthma (SSRA) is a serious clinical problem in asthma management. Affected patients have severe clinical symptoms, worsened quality of life, and do not respond to steroid, a mainstay steroid treatment of asthma. Thus, effective therapies are urgently needed. Exosomes derived from mesenchymal stem cell (MSC-Exo) has become attractive candidates for the lung inflammatory diseases through its immunomodulatory effects. In this study, we explored the therapeutic effects of MSC-Exo in SSRA and identified the therapeutic mechanism of MSC-Exo. Method Exosomes from human umbilical cord mesenchymal stem cell (hUCMSC) were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis and flow cytometry analysis. Effects of MSC-Exo on airway hyper responsiveness (AHR), inflammation, histopathology, and macrophage polarization in SSRA in mice were evaluated. Systematic depletion of macrophages determined the role of macrophages in the therapeutic effect of SSRA in mice. LPS-stimulated RAW 264.7 cell model was constructed to determine the underlying mechanism of MSC-Exo on macrophage polarization. qRT-PCR, Western blotting, immunofluorescence, and flow cytometry were performed to evaluate the expression of M1 or M2 markers. Tandem mass tags (TMT)-labeled quantitative proteomics were applied to explore the central protein during the regulation effect of MSC-Exo on macrophage polarization. Knockdown and overexpression of TRAF1 were used to further clarify the role of the central protein on macrophage polarization. Result We successfully isolated and characterized exosomes from hUCMSCs. We verified that the intratracheal administration of MSC-Exo reversed AHR, histopathology changes, and inflammation in SSRA mice. Systematic depletion of macrophages weakened the therapeutic effect of MSC-Exo. We found that MSC-Exo treatment inhibited M1 polarization and promoted M2 polarization in LPS-stimulated RAW 264.7 cells. Subsequently, tumor necrosis factor receptor-associated factor 1 (TRAF1) was determined as the central protein which may be closely related to the regulation of macrophage polarization from TMT-labeled quantitative proteomics analysis. Knockdown and overexpression of TRAF1 demonstrated that the effect of MSC-Exo treatment on macrophage polarization, NF-κB and PI3K/AKT signaling was dependent on TRAF1. Conclusion MSC-Exo can ameliorate SSRA by moderating inflammation, which is achieved by reshaping macrophage polarization via inhibition of TRAF1.

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