Alveolar Macrophages in the Resolution of Inflammation, Tissue Repair, and Tolerance to Infection

Allard, Benoît; Panariti, Alice; Martin, James G.

doi:10.3389/fimmu.2018.01777

Cited by 247 publications

(216 citation statements)

References 78 publications

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“…Expression of myeloid cell genes in the airway also correlated with a signature of oxidative metabolism, which is characteristic of M2 macrophages and typically associated with control of tissue damage (Viola et al, 2019). However, in the context of pulmonary infection, polarization of AMs toward an anti-inflammatory M2 phenotype was found to promote continued inflammation, suggesting that these MΦs may not be effective at resolving anti-viral immunity (Allard et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Transcriptomic Analysis of COVID-19 Blood, Lung, and Airway

Daamen

Bachali

Owen

et al. 2020

Preprint

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SARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients.3 1 Methods Read quality, trimming, mapping and summarizationPublicly available data sets used in this study are listed in Table S1. RNA-seq data were processed using a consistent workflow using FASTQC, Trimmomatic, STAR, Sambamba, and featureCounts. As described below SRA files were downloaded and converted into FASTQ format using SRA toolkit. Read ends and adapters were trimmed with Trimmomatic (v0.38) using a sliding window, ilmnclip, and headcrop filters. Both datasets were head cropped at 6bp and adapters were removed before read alignment.Reads were mapped to the human reference genome hg38 using STAR, and the .sam files were converted to sorted .bam files using Sambamba. Read counts were summarized using the featureCounts function of the Subread package (v1.61.)The RNA-seq tools are all free, open source programs available at the following web addresses SRA toolkit -https

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Section: Discussionmentioning

confidence: 99%

Comprehensive Transcriptomic Analysis of COVID-19 Blood, Lung, and Airway

Daamen

Bachali

Owen

et al. 2020

Preprint

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“…These findings, however, should be treated with caution, as genetic depletion of macrophages induces their death via necrosis and may induce tissue damage on its own (21). Single-cell RNA-Seq data may identify specific markers that can be used to more precisely target distinct macrophage populations to dissect their contributions to tissue injury and repair (76,(102)(103)(104)(105).…”

Section: The Journal Of Clinical Investigationmentioning

confidence: 99%

The role of macrophages in the resolution of inflammation

Watanabe

Alexander

Misharin

et al. 2019

Journal of Clinical Investigation

632

452

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“…6. Blockade of EZH2 with 3-DZNeP suppresses the in vitro EMT in co-cultured BALF and mouse lung epithelial cell lines through regulation of the TGF-β/Smad signaling It has been reported that alveolar macrophages can interact with several other cell types such as epithelial, endothelial and immune cells during tissue repair and regeneration and brosis [24] , however the underlying mechanism remains incompletely understood. Since we observed that the M2-like macrophages were elevated while EMT was suppressed in the alveolus of 3-DZNeP-treated brotic mice, we hypothesized that there existed a crosstalk between macrophages and epithelial cells in the alveolar microenvironment.…”

Section: -Dznep Suppresses the In Vivo Emt By Inhibiting Activationmentioning

confidence: 99%

Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype

Bao

Liu

et al. 2020

Preprint

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Background: We recently reported histone methyltransferase enhancer of zeste homolog 2 (EZH2) as a key epigenetic regulator that contributes to the dysfunction of innate immune responses to sepsis and subsequent lung injury by mediating the imbalance of macrophage polarization. However, the role of EZH2 in acute respiratory distress syndrome (ARDS)-associated fibrosis remains poorly understood. Methods: In this study, we investigated the role and mechanisms of EZH2 in pulmonary fibrosis in a murine model of LPS-induced ARDS and in ex-vivo cultured alveolar macrophages (MH-S) and mouse lung epithelial cell line (MLE-12) by using 3-deazaneplanocin A (3-DZNeP) and EZH2 the small interfering (si) RNA. Results: We found that treatment with 3-DZNeP significantly ameliorated the LPS-induced direct lung injury and fibroproliferation by blocking the epithelial to mesenchymal transition (EMT) through transforming growth factor-β1 (TGF-β1)/Smad signaling pathway and regulating shift of macrophage phenotypes. In the ex-vivo polarized alveolar macrophages cells, treatment with EZH2 siRNA or 3-DZNeP suppressed the M1 while promoted the M2 macrophage differentiation through modulating the STAT/SOCS signaling pathway and activating PPAR-γ. Moreover, we identified that blockade of EZH2 with 3-DZNeP suppressed EMT in co-cultured bronchoalveolar lavage fluid (BALF) and mouse lung epithelial cell line through down-regulation of TGF-β1, TGF-βR1, Smad2 while up-regulation of Smad7 expression. Conclusions: These results indicate that EZH2 is involved in the pathological process of ARDS-associated pulmonary fibrosis. Targeting EZH2 may be a potential therapeutic strategy to prevent and treat pulmonary fibrosis post ARDS.

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Alveolar Macrophages in the Resolution of Inflammation, Tissue Repair, and Tolerance to Infection

Cited by 247 publications

References 78 publications

Comprehensive Transcriptomic Analysis of COVID-19 Blood, Lung, and Airway

Comprehensive Transcriptomic Analysis of COVID-19 Blood, Lung, and Airway

The role of macrophages in the resolution of inflammation

Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype

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