Peritoneal macrophage heterogeneity in decompensated liver cirrhosis
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ABSTRACT:
PROVIDER: PRJNA514059 | ENA |
REPOSITORIES: ENA
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Project description:Peritoneal macrophages (PM) are thought to regulate peritoneal inflammation and control bacterial infections in decompensated liver cirrhosis. The aim of this study was to characterize human PM heterogeneity. Employing CD206 surface expression, we identified subsets of human large (LPM) and small (SPM) PM, which differed in granularity and maturation states. FACS-sorted LPM from patients with decompensated cirrhosis revealed discrete transcriptome clusters, comprising more than 4000 differentially regulated genes involved in cell cycle, metabolism, and immune signaling.
2020-03-24 | GSE124878 | GEO
Project description:Objectives Non-invasive staging of decompensated cirrhosis is an unmeet clinical need. The aims of this study were to characterize and validate a novel miRNA signature to stage decompensated cirrhosis and predict the portal pressure and cardiac dysfunction response to non-selective beta-blockers (NSBB). Design Serum samples from patients with decompensated cirrhosis (n=36) and healthy controls (n=36) were tested for a novel signature of five miRNAs (miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p) identified in the secretome of primary human hepatocytes, and three miRNAs (miR-192-5p, miR-34a-5p and miR-29a-5p) previously discovered as biomarkers of chronic liver disease. All patients had ascites, that was refractory in 18 (50%), and were placed on NSBB for variceal bleeding prophylaxis. In all patients, serum miRNAs, hepatic venous pressure gradient (HVPG), and echocardiogram study was performed before and 1 month after NSBB. Results Cirrhotic patients had lower serum levels of miR-429, miR-885-5p, miR-181b-5p, miR-122-5p, miR-192-5p and miR-29a-5p (p<0.05). miR-452-5p and miR-429 expression were lower in NSBB responders (p=0.006). miR-181b-5p expression was greater in refractory- than in diuretic sensitive ascites (p=0.008) and correlated with serum creatinine. miR-452-5p and miR-885-5p were inversely correlated with baseline systemic vascular resistance (ρ=-0.46 p=0.007; and ρ=-0.41 p=0.01 respectively), and with diminished systolic contractility in patients with refractory ascites after NSBB (ρ=-0.55 p=0.02; and ρ=-0.55 p=0.02, respectively). Conclusion Analysis of a miRNA signature in serum distinguishes patients with decompensated cirrhosis who show more severe systemic circulatory dysfunction and compromised systolic function after beta-blockade, and those more likely to benefit from NSBB.
2021-02-10 | GSE150867 | GEO
Project description:Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesising that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage sub-populations. The proportion of CRIgHi macrophages differed between patients, and in the same patient over time, and a high proportion of CRIgHi macrophages was associated with reduced disease severity (Model for End Stage Liver Disease (MELD)) score. As compared to CRIgLow macrophages, CRIgHi macrophages were highly phagocytic and displayed enhanced antimicrobial effector activity. Transcriptional profiling by RNA Sequencing and comparison with human macrophage and murine peritoneal macrophage expression signatures highlighted similarities between CRIgHi cells, human macrophages and mouse F4/80Hi resident peritoneal macrophages, and between CRIgLow macrophages, human monocytes and mouse F4/80Low monocyte-derived peritoneal macrophages. These data suggest CRIgHi and CRIgLow macrophages may represent a tissue-resident population and a monocyte-derived population, respectively. In conclusion, ascites fluid macrophage subset distribution and phagocytic capacity is highly variable between patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients.
2017-08-22 | GSE79833 | GEO
Project description:MOLECULAR PROFILING OF DECOMPENSATED CIRRHOSIS BY A NOVEL microRNA SIGNATURE
| PRJNA633887 | ENA
Project description:Transcriptome analysis of two population of peritoneal mononuclear phagocytes (CD14+ macrophages and CD1c+ dendritic cells) in peritoneal dialysis effluent from stable (infection-free) peritoneal dialysis patients.
2017-01-23 | E-MTAB-5439 | biostudies-arrayexpress
Project description:Bone marrow derived macrophage vs peritoneal macrophage
| PRJNA414129 | ENA
Project description:In this study, we profiled the precision N-glycoproteome of the murine peritoneal macrophage under different stimulation.
2021-06-12 | PXD026629 | Pride
Project description:Immunometabolism is a rapidly growing field, which has led to greater understanding of innate immune cell functions. Macrophages are at the core of this research: polarized subsets of in vitro-derived cells reportedly utilize select metabolic pathways to maintain their phenotype. However, relevance of these in vitro studies to the in vivo setting is not known, and metabolic requirements are likely dependent on unique physiological and cellular metabolic environments. Here we define the metabolic requirements of peritoneal tissue-resident macrophages, the accessibility of these metabolites to cells in the peritoneum, and we dissect the role of this unique environment in maintaining a crucial macrophage function. We find that the peritoneal cavity is enriched in amino acids, most notably glutamate. Peritoneal tissue-resident macrophages have an extraordinarily large mitochondrial capacity compared with other phagocytes; this is primarily fueled by glutaminolysis, which is additionally required to maintain an extensive respiratory burst. Glutaminolysis fuels the electron transport chain, which is enhanced during tissue-resident macrophage respiratory burst via a switch to dependence of mitochondrial complex-II. This is not dependent on the level of NADPH, but requires p47 maintained NADPH-oxidase activity. Therefore, we propose that tissue-resident macrophages exploit their unique metabolic niche by implementing their glutamine-fueled mitochondrial-rich phenotype to sustain respiratory burst to assault pathogens, showing that cell-specific metabolic underpinning is important for function. Importantly, we also find that glutamine is required for the respiratory burst in human monocytes, which highlights that metabolites are not species-specific and can be the link between cellular mechanism in mouse and man.
2017-10-13 | GSE104920 | GEO
Project description:Human serum albumin (HSA) is an emerging treatment for preventing excessive systemic inflammation and organ failure(s) in patients with acutely decompensated (AD) cirrhosis. Here, we investigated the molecular mechanisms underlying the immunomodulatory properties of HSA. Administration of HSA to patients with AD cirrhosis with elevated circulating bacterial DNA (CpG-DNA) was associated with reduced plasma cytokine levels. In isolated leukocytes, HSA abolished CpG-DNA-induced cytokine expression and release independently of its oncotic and scavenging properties. Similar anti-inflammatory effects were observed with recombinant human albumin. HSA exerted widespread changes on the immune cell transcriptome, specifically in genes related to the endosomal compartment involved in cytosolic DNA sensing and type I interferon responses. Flow cytometry and confocal microscopy analyses revealed that HSA was taken up by leukocytes and internalized in vesicles positively stained with EEA1, a marker of early endosomes. Indeed, HSA and CpG-DNA colocalized in endosomes, the compartment where CpG-DNA binds to TLR9, its cognate receptor. Furthermore, HSA also inhibited poly-(I:C)- and LPS-induced IRF3 phosphorylation and TRIF-mediated responses, which are exclusive of endosomal TLR3 and TLR4 signaling, respectively. The immunomodulatory actions of HSA did not compromise leukocyte defensive mechanisms such as phagocytosis, efferocytosis and intracellular ROS production. The in vitro immunomodulatory effects of HSA were confirmed in vivo in analbuminemic humanized FcRn transgenic mice. In conclusion, these findings indicate that HSA internalizes in immune cells and modulates their responses through interaction with endosomal TLR signaling, thus providing a mechanism for the benefits of HSA infusions in patients with cirrhosis.
2023-03-02 | GSE146462 | GEO
Project description:Peritoneal dialysis (PD) is a successful renal replacement therapy for end-stage renal disease that effectively improves the quality of life. Long-term PD causes epithelial mesenchymal transformation (MMT) of peritoneal mesothelial cells, leading to peritoneal fibrosis which reduces the efficiency of PD. Macrophages are considered players in the onset and perpetuation of peritoneal injury. Yet, the mechanisms employed by macrophage-mesothelial cells communication to regulate peritoneal fibrosis are not fully elucidated resulting in lack of disease-modified drugs. This study analyzes the role of macrophage-mesothelial cell communication by intraperitoneal injection of macrophage derived exosomes in PD model rats. These results show that macrophages secrete exosomal miR-204-5p that directly targets Foxc1, leading to the activation of MMT in mesothelial cells. The data also shows that intraperitoneal injection of dissolved AS-IV can improve MMT by altering macrophage derived exosomal miRNAs. This study indicates that intercellular crosstalk between peritoneal macrophages and mesothelial cells is mediated by macrophage derived miR-204-5p-containing exosomes that control the MMT progression, providing AS-IV for prevention and treatment of PD induced peritoneal fibrosis. Our results demonstrate, for the first time, a novel role of the AS-IV on miR-204-5p/Foxc1/β-catenin axis in improving peritoneal fibrosis in vivo and vitro.
2023-01-01 | GSE165342 | GEO