Contribution of the scavenger receptor MARCO to TLR-induced activation of dendritic cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE55068 | GEO | 2014/02/18
SECONDARY ACCESSION(S): PRJNA238394
REPOSITORIES: GEO
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Project description:To gain additional insight into the role of MARCO in dendritic cell activation and function, we profiled transcriptomes of mouse splenic dendritic cells obtained from MARCO deficient mice and their wild type counterparts under resting and activating conditions. Pure dendritic cells from the spleens of WT and MARCO KO mice were cultured overnight in PBS or Lipopolysaccharide (LPS). Gene expression profiling was performed using Affymetrix platform.
2014-02-18 | E-GEOD-55068 | biostudies-arrayexpress
Project description:The scavenger receptor MARCO mediates macrophage recognition and clearance of pathogens and their polyanionic ligands. However, recent studies demonstrate MARCO expression and function in dendritic cells, suggesting MARCO might serve to bridge innate and adaptive immunity. To gain additional insight into the role of MARCO in dendritic cell activation and function, we profiled transcriptomes of mouse splenic dendritic cells obtained from MARCO deficient mice and their wild type counterparts under resting and activating conditions. In silico analysis uncovered major alterations in gene expression in MARCO deficient dendritic cells resulting in dramatic alterations in key dendritic cell-specific pathways and functions. Specifically, changes in CD209, FCGR4 and Complement factors can have major consequences on DC-mediated innate responses. Notably, these perturbations were magnified following activation with the TLR-4 agonist lipopolysaccharide. To validate our in silico data, we challenged DC's with various agonists that recognize all mouse TLRs and assessed expression of a set of immune and inflammatory marker genes. This approach identified a differential contribution of MARCO to TLR activation and validated a major role for MARCO in mounting an inflammatory response. Together, our data demonstrate that MARCO differentially affects TLR-induced DC activation and suggest targeting of MARCO could lead to different outcomes that depend on the inflammatory context encountered by DC.
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Project description:Scavenger receptors on the cell surface of macrophages play an important role in host defence through their ability to bind microbial ligands and induce phagocytosis. Concurrently, signal transduction pathways are initiated that aid in defence mechanisms against the invading microbe. Here we report on the function of scavenger receptor Marco (macrophage receptor with collagenous structure) during infection of zebrafish embryos with Mycobacterium marinum, a close relative of Mycobacterium tuberculosis. Morpholino knockdown demonstrates that Marco is required for the rapid phagocytosis of M. marinum following intravenous infection. Furthermore, gene expression analysis shows that Marco controls the initial transient pro-inflammatory response to M. marinum and remains a determining factor for the immune response signature at later stages of infection. Increased bacterial burden following marco knockdown indicates that this scavenger receptor is important for control of M. marinum growth, likely due to delayed phagocytosis and reduced pro-inflammatory signalling observed under conditions of Marco deficiency
2014-08-06 | GSE58230 | GEO
Project description:Macrophages are the most common infiltrating immune cells in glioblastoma (GBM), and play a wide variety of pro-tumor and anti-tumor roles. However, the different subpopulations of macrophages and their effects on the tumor microenvironment remain poorly understood. Here, we combine new and previously-published single-cell RNA-seq data from 86,279 single cells from a total of 63 gliomas to profile 17,774 individual macrophages. Unsupervised clustering revealed an anti-inflammatory subpopulation of macrophages characterized by expression of MARCO (macrophage receptor with collagenous structure), a gene which has not been previously well-characterized in gliomas. MARCO is almost exclusively expressed in macrophages of IDH1-wildtype GBM rather than IDH1-mutated GBM or lower-grade gliomas. Previous studies have implicated MARCO as an unfavorable marker in melanoma and non-small-cell lung cancer; here, we find that bulk MARCO expression is associated with worse prognosis in TCGA glioblastomas, and associates with the mesenchymal expression subtype. Our single-cell analysis shows that this previously-reported mesenchymal signature primarily arises from MARCO-expressing macrophages. These MARCO-expressing macrophages differentially over-express gene sets related to hypoxia and the epithelial-mesenchymal transition, and under-express gene sets related to inflammation and antigen presentation. We show evidence that MARCO-expressing macrophages are recruited from the blood (as opposed to being resident microglia), and paired single-cell analysis of tumor and myeloid cells demonstrate that this recruitment may be driven by known chemoattractant factors. Furthermore, MARCO expression is significantly altered over the course of treatment with PD1 checkpoint inhibitors. These findings illustrate a novel myeloid subpopulation that drives tumor progression in glioblastomas, and suggest potential therapeutic targets to prevent their recruitment glioblastoma.
2020-12-23 | GSE141383 | GEO
Project description:While viremia in the vertebrate host is a critical determinant of arboviral reservoir competency, transmission efficiency, and disease severity, immune mechanisms that control arboviral viremia are poorly defined. Here, we identify critical roles for the scavenger receptor MARCO in controlling viremia during arthritogenic alphavirus infections in mice. Following subcutaneous inoculation, alphavirus particles drain via the lymph and are rapidly captured by MARCO+ lymphatic endothelial cells (LECs) in the draining lymph node (dLN), limiting viral spread to the bloodstream. Upon reaching the bloodstream, MARCO-expressing Kupffer cells in the liver remove circulating alphavirus particles, limiting viremia and further viral dissemination. MARCO-mediated accumulation of alphavirus particles in the lymph node and liver has important implications as viremia and viral tissue burdens are elevated in MARCO-/- mice and disease outcomes are more severe. These findings uncover a previously unrecognized pathogen scavenging role for LECs and improve our mechanistic understanding of viremia control during arboviral infections.
2021-09-10 | GSE174667 | GEO
Project description:Mouse splenic dendritic cells are divided into different subsets based on their phynotype. CD8α+ and CD8α- dendritic cells play different roles against pathogens. Cross-presentation is essential for immune defense against viruses, tumors and intracellular bacteria and CD8α+ DCs are more potent in cross-presentation compared to CD8α- DCs. We used microarrays to detail the global gene expression to analyze the underlying mechanism in CD8α+ dendritic cells cross-presentation Splenic CD8α+ and CD8α- dendritic cells were sorted by flow-cytometer for RNA extraction and hybridization on Affymetrix microarrays. Thirty C57BL/6J mice were sacrified for the splenic cells, splenic DCs were enriched by negtive selection, then CD8α+ and CD8α- dendritic cells were seprated based on CD11c and CD8α markers.
2016-07-27 | E-GEOD-64124 | biostudies-arrayexpress
Project description:Whereas macrophages use the scavenger receptor MARCO primarily in antimicrobial immunity by interacting with both exogenous and endogenous environments, in dendritic cells (DCs) MARCO is believed to pleiotropically link innate to adaptive immunity. MARCO exerts a significant modulatory effect on TLR-induced DC activation, thus offering novel avenues in cancer immunotherapy.
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Project description:To investigate the expression of glycosyltransferases in dendritic cells and the changes in expression associated with maturation. Healthy normal donor RNA preparations from Resting macrophages (Macro), LPS-mature dendritic cells (LPSMDC), IL-15 immature dendritic cells (IL15DC), Dexamethasone immature dendritic cells (DxMDC) from 2 different donors.
2011-04-29 | E-GEOD-28934 | biostudies-arrayexpress
Project description:To investigate the transcription start site of MARCO-TST in triple negative breast cancer, we performed endogenous purification of H3K27ac and H3K4me3 under ChIP conditions, followed by high throughput sequencing.
2022-09-28 | GSE214133 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE22127: Expression profiling of small intestine lamina propria dendritic cells GSE22128: Expression profiling of splenic dendritic cells Dendritic cells play a vital role in initiating robust immunity against pathogens as well as maintaining immunological tolerance to self antigens, food antigens and intestinal commensals. However, the intracellular signaling networks that program DCs to become tolerogenic are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified intestinal lamina propria DCs (CD11c+ CD11b+ DCs and CD11c+ CD11b- DCs) and compared it to splenic DCs (CD11c+ DC), from mice. We sought to determine the unique genetic profile of small intestine lamina propria CD11c+ cells compared to splenic CD11c+ cells. We performed a meta-analysis using the expression profiles of Intestinal lamina propria CD11c+ CD11b+ DCs (GSM550122), Intestinal lamina propria CD11c+ CD11b- DCs (GSM550121) and Splenic CD11c+ DCs (GSM550126). This study combined and re-normalized the microarray data from GSE22127 and GSE22128 studies. Refer to individual Series for additional details
2010-06-16 | E-GEOD-22136 | biostudies-arrayexpress