Expression of the mannose receptor (CD206) defines distinct populations of human colonic macrophages in health and inflammatory bowel disease
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PROVIDER: PRJNA511766 | ENA |
REPOSITORIES: ENA
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Project description:BACKGROUND & AIMS: Intestinal mononuclear phagocytes (MNP) are phenotypically similar, but have different functions. Macrophages contribute to the pathogenesis of inflammatory bowel disease (IBD). To understand this contribution it is necessary to distinguish macrophages from other MNPs, and identify functionally-different macrophage populations. We aimed to accurately identify intestinal macrophage populations, and to ascertain their functions in patients with inflammatory bowel disease (IBD). METHODS: We developed 12-parameter flow cytometry protocols to identify and characterise human intestinal MNPs. We then used RNA sequencing, qPCR, and flow cytometry to analyse colonic biopsies from patients with CD, UC, or non-inflamed controls, in a cross-sectional study. RESULTS: We unambiguously differentiate macrophage populations (CD45+CD64+ HLA-DR+) from dendritic cells (CD45+CD64- HLA-DR+ CD11c;). We identify two distinct subsets within the macrophage population, differentiated by their expression of the mannose receptor, CD206. Further examination of these macrophage sub-populations showed that CD206+ macrophages expressed markers consistent with a mature macrophage phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of Trem1. On the contrary, CD64+ HLA-DR- CD206- cells appear to be semi-mature intermediaries in the development of mature intestinal macrophages from their monocyte precursors. CONCLUSIONS: We identified and purified MNP and macrophage populations from human intestinal lamina propria. Thorough characterisation reveals that human colonic macrophages appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature they lose their proliferative properties and acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD.
2018-12-26 | GSE124350 | GEO
Project description:To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs. We used these protocols to purify and characterize colonic macrophages from colonic tissue from patients with Crohn's disease (CD), ulcerative colitis (UC), or non-inflamed controls, in a cross-sectional study. We identify macrophage populations (CD45+CD64+ HLA-DR+) and describe two distinct subsets, differentiated by their expression of the mannose receptor, CD206. CD206+ macrophages expressed markers consistent with a mature phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of TREM1. CD206- macrophages appear to be less mature, with features more similar to their monocytic precursors. We identified and purified macrophage populations from human colon. These appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature, they acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD.
| S-EPMC8490356 | biostudies-literature
Project description:To explore the influence of glycosylation on mannose receptor (MR) binding to glycan ligands, we used the mouse CTLD4-7, fused to the Fc-portion of human IgG (MR-Fc) and human full-length MR. A detailed N- and O-glycopeptide analysis was performed using tryptic glycopeptides. In addition the samples were partially treated with different exoglycosidases to increase glycopeptide coverage.
2023-03-11 | PXD034781 | Pride
Project description:Clostridioides difficile CD206 Genome sequencing and assembly
| PRJNA85781 | ENA
Project description:Dysregulated proteolysis plays a pivotal role in the pathophysiology of inflammatory bowel disease. Nonetheless, the identity of overactive proteases released by human colonic mucosa remains unknown. Herein, we employed a serine protease-targeted activity-based probe (ABP) coupled with mass spectral analysis to identify active forms of proteases secreted by the colonic mucosa of healthy volunteers and inflammatory bowel disease patients. With this approach, we identified seven active serine proteases: cathepsin G, plasma kallikrein, plasmin, tryptase, chymotrypsin-like elastase 3A, aminopeptidase B, and thrombin. Furthermore, cathepsin G and thrombin were overactive in supernatants from inflammatory bowel disease patients once compared to healthy volunteers.
2018-05-18 | PXD009450 | Pride
Project description:CD206 is a common marker of a putative immunosuppressive ‘M2’ state in tumor-associated macrophages (TAMs). We made a novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs. Early depletion of CD206+ macrophages and monocytes (Mono/Macs) led to the indirect loss of conventional type I dendritic cells (cDC1), CD8 T cells and NK cells in tumors. CD206+ TAMs robustly expressed CXCL9, contrasting with stress-responsive Spp1-expressing TAMs and immature monocytes, which became prominent with early depletion. CD206+ TAMs differentially attracted activated CD8 T cells, and the NK and CD8 T cells in CD206-depleted tumors were deficient in Cxcr3, and cDC1-supportive Xcl1 and Flt3l expression. Disrupting this key anti-tumor axis decreased tumor control by antigen-specific T cells in mice. In human cancers, a CD206Replete, but not a CD206Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, cDC1 and NK signatures, and associated with better survival. These findings negate the unqualified classification of CD206+ ‘M2-like’ macrophages as immunosuppressive.
2024-11-08 | GSE281345 | GEO
Project description:In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans, expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We found that extravascular haemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking haemoglobin S. This proteomics analysis is to prove the identify of high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin.
2021-03-17 | PXD024022 | Pride
Project description:This study explored the regulatory effect of D-mannose on host immunometabolic responses after viral infection. The results showed that D-mannose can compete with glucose for transporters and hexokinase, inhibiting glycolysis, reducing mitochondrial reactive oxygen species and succinate-induced HIF-1α, thereby reducing virus-induced inflammatory cytokine production. Even with delayed combinatorial treatment of D-mannose and antiviral monotherapy after viral infection, a synergistic effect was still observed in mouse models. Phosphomannose isomerase (PMI) activity determines the benefits of D-mannose, as simultaneous PMI depletion and mannose supplementation impaired cell viability. PMI inhibition can suppress replication of various viruses by affecting host and viral surface protein glycosylation. However, D-mannose does not inhibit PMI activity or viral fitness. In summary, PMI-centered therapeutic strategies can eliminate viral infections, while D-mannose treatment reprograms glycolysis to control collateral damage.
2024-02-13 | GSE255332 | GEO
Project description:The direct and indirect effects of targeting specific tumor-associated macrophage (TAM) subsets in cancer are not well-defined. TAM targeting strategies are frequently based on the ‘M1’ or ‘M2’ polarization categories, even as substantial data challenges this binary modeling of macrophage cell state. One molecule consistently referenced as a delineator of a putative immunosuppressive ‘M2’ state is the surface protein CD206. We thus made a novel conditional CD206 (Mrc1) knock-in mouse to specifically visualize and/or deplete CD206+ TAMs and assess their correspondence with pro-tumoral immunity. Early, but not late depletion of CD206+ macrophages and monocytes (here, ‘Mono/Macs’) led to an indirect loss of a key anti-tumor network of NK cells, conventional type I dendritic cells (cDC1) and CD8 T cells. Among myeloid cells, we found that the CD206+ TAMs are the primary producers of CXCL9, and able to differentially attract activated CD8 T cells. In contrast, a population of stress-responsive TAMs (“Hypoxic” or Spp1+) and immature monocytes, which lack CD206 expression and become prominent following early depletion, expressed markedly diminished levels of CXCL9. Those NK and CD8 T cells which enter CD206-depleted tumors express vastly reduced levels of the corresponding receptor Cxcr3, the cDC1-attracting chemokine Xcl1 and cDC1 growth factor Flt3l transcripts. Consistent with the loss of this critical network, early CD206+ TAM depletion decreased tumor control by antigen specific CD8 T cells in mice. Likewise, in humans, the CD206Replete, but not the CD206Depleted Mono/Mac gene signature correlated robustly with CD8 T cell, NK cell and stimulatory cDC1 gene signatures and transcriptomic signatures skewed towards CD206Replete Mono/Macs associated with better survival. Together, these findings negate the unqualified classification of CD206+ ‘M2-like’ macrophages as immunosuppressive and provide further evidence of the context-dependence of macrophage function in tumors.
2024-11-08 | GSE281471 | GEO
Project description:Melatonin has been reported to improve NAFLD, exploring the underlying mechanisms will be beneficial for better treatment of NAFLD. CDHFD- and MCD-fed mice with melatonin intervention exhibited significantly decreased liver steatosis, lobular inflammation, and focal liver necrosis. Single-cell RNA sequencing revealed melatonin selectively inhibited proinflammatory CCR3+ MoMFs, and upregulated anti-inflammatory CD206+ MoMFs in NAFLD mice. Hepatic infiltrated CCR3+CD14+ MoMFs is also significantly increased in patients with NAFLD. Mechanistically, melatonin receptor independent BTG2-ATF4 signaling plays a vital role in the regulation of CCR3+ MoMFs endoplasmic reticulum stress, survival, and proinflammation by melatonin. In contrast, melatonin upregulated CD206+ MoMFs survival and polarization via MT1/2 receptors. Melatonin stimulation also regulates human CCR3+ MoMFs and CD206+ MoMFs survival and inflammation in vitro. Furthermore, CCR3 depletion antibody monotherapy decreased liver inflammation and improved NAFLD in mice. Thus, Therapies targeting CCR3+ MoMFs may have potential benefits in NAFLD treatment.
2023-06-04 | GSE204821 | GEO