Ontology highlight
ABSTRACT:
PROVIDER: PRJNA792491 | ENA |
REPOSITORIES: ENA
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Project description:This experiment aimed at characterising the modulatory role of murine induced Neural Stem Cells (iNSCs) and Neural Stem Cells (NSCs) on macrophages (MPs) exposed to LPS in vitro. Naïve MPs were polarized into an M1-like phenotype with LPS, and then co-cultured with 1:1 ratios of iNSCs in a trans-well system that avoids cell-to-cell contacts. Naïve MPs, LPS-stimulated MPs and LPS-stimulated MPs co-cultured with NSCs were used as controls.
2018-01-01 | E-MTAB-5579 | biostudies-arrayexpress
Project description:Multiple myeloma (MM) is a plasma cell malignancy characterized by the presence of multiple foci in the skeleton. These distinct tumor foci indicate cycles of tumor growth and dissemination that seed new clusters and drives disease progression. Utilizing an intra-tibial Vk*MYC murine myeloma, we found that CD169 + radiation-resistant, tissue-resident macrophages (MPs) were critical for myeloma early dissemination and disease progression. While depletion of these MPs had no effect on tumor proliferation, it reduced myeloma BM egress and spreading to other bones, which improved overall survival as a single therapy and in combination with BM transplantation. Myeloma dissemination correlated with an increased inflammatory signature in BM MPs, as well as production of IL-6 and TNFα by tumor-associated MPs (TAMs). Exogenous i.v. IL-6 and TNFa could trigger myeloma intravasation in the BM by increasing vascular leakiness in the BM, and by enhancing myeloma motility by reducing CD138 adhesion. Moreover, mice lacking IL-6 had defects in myeloma dissemination as in MP-depleted recipients. While in TNFa or TNFaR deficient mice had defects in MM dissemination, engraftment was also impaired. These effects on myeloma dissemination required production of cytokines in the radiation-resistant compartment, containing these radiation-resistant BM MPs. Taken together, we propose BM egress of myeloma cells is regulated by localized inflammation in foci, driven in part by CD169 + MPs.
2021-06-09 | GSE176385 | GEO
Project description:Microparticles (MP) are small membranous particles (100-1000 nm) released under normal steady-state conditions and are thought to provide a communication network between host cells. Previous studies demonstrated that Mycobacterium tuberculosis (M.tb) infection of macrophages increased the release of MPs, and these MPs induced a proinflammatory response from uninfected macrophages in vitro and in vivo following their transfer into uninfected mice. To determine how M.tb infection modulates the protein composition of the MPs, and if this contributes to their proinflammatory properties, we compared the proteomes of MPs derived from M.tb-infected (TBinf-MP) and uninfected human THP-1 monocytic cells. MP proteins were analysed by GeLC-MS/MS with spectral counting revealing 68 proteins with statistically significant differential abundances. The 42 proteins increased in abundance in TBinf-MPs included proteins associated with immune function (7), lysosomal/endosomal maturation (4), vesicular formation (12), nucleosome proteins (4) and antigen processing (9). Prominent among these were the type I interferon inducible proteins, ISG15, IFIT1, IFIT2, and IFIT3. Exposure of uninfected THP-1 cells to TBinf-MPs induced increased gene expression of isg15, ifit1, ifit2, and ifit3 and the release of proinflammatory cytokines. These proteins may regulate the proinflammatory potential of the MPs and provide candidate biomarkers for M.tb infection.
2022-02-28 | PXD002026 | Pride
Project description:Tuberculosis (TB) remains a prevalent and lethal infectious disease. The glycobiology associated with Mycobacterium tuberculosis infection of frontline alveolar macrophages is still unresolved. Herein, we investigated the regulation of protein N-glycosylation in human macrophages and their secreted microparticles (MPs) used for intercellular communication upon M. tb infection. LC-MS/MS-based proteomics and glycomics were performed to monitor the regulation of glycosylation enzymes and receptors and the N-glycome in in vitro-differentiated macrophages and in isolated MPs upon M. tb infection. Infection promoted a dramatic regulation of the macrophage proteome. Most notably, significant infection-dependent down-regulation (4-26 fold) of 11 lysosomal exoglycosidases e.g. β-galactosidase, β-hexosaminidases and α-/β-mannosidases was observed. Relative weak infection-driven transcriptional regulation of these exoglycosidases and a stronger augmentation of the extracellular hexosaminidase activity demonstrated that the lysosome-centric changes may originate predominantly from infection-induced secretion of the lysosomal content. The macrophages showed heterogeneous N-glycan profiles and displayed significant up-regulation of complex-type glycosylation and concomitant down-regulation of paucimannosylation upon infection. Complementary intact N-glycopeptide analysis supported a subcellular-specific manipulation of the glycosylation machinery and altered glycosylation patterns of lysosomal N-glycoproteins within infected macrophages. Interestingly, the corresponding macrophage-derived MPs displayed unique N-glycome and proteome signatures supporting a preferential packaging from plasma membranes. The MPs were devoid of infection-dependent N-glycosylation signatures, but interestingly displayed increased levels of the glyco-initiating oligosaccharyltransferase complex and associated α-glucosidases that correlated with increased formation, N-glycan precursor levels and N-glycan density of infected MPs. In conclusion, this system-wide study provides new insight into the host- and pathogen-driven N-glycoproteome manipulation of macrophages in TB.
2024-01-26 | PXD005169 | Pride
Project description:Dendritic cells (DCs) and macrophages (MPs) are important for immunological homeostasis in the colon. We found that F4/80hi CX3CR1hi (CD11b+CD103-) cells account for 80% of mouse colonic lamina propria (cLP) MHC-IIhi cells. Both CD11c+ and CD11c- cells within this population were identified as MPs based on multiple criteria, including a MP transcriptome revealed by microarray analysis. These MPs constitutively released high levels of IL-10 at least partially in response to the microbiota via an MyD88-independent mechanism. In contrast, cells expressing low to intermediate levels of F4/80 and CX3CR1 were identified as DCs, based on phenotypic and functional analysis and comprise three separate CD11chi cell populations: CD103+CX3CR1-CD11b- DCs, CD103+CX3CR1-CD11b+ DCs and CD103-CX3CR1intCD11b+ DCs. In non-inflammatory conditions, Ly6Chi monocytes differentiated primarily into CD11c+, but not CD11c- MPs. In contrast, during colitis, Ly6Chi monocytes massively invaded the colon and differentiated into pro-inflammatory CD103-CX3CR1intCD11b+ DCs, which produced high levels of IL-12, IL-23, iNOS and TNF. These findings demonstrate the dual capacity of Ly6Chi blood monocytes to differentiate into either regulatory MPs or inflammatory DCs in the colon, and that the balance of these immunologically antagonistic cell types is dictated by microenvironmental conditions. FACS sorted expression from normal controls
2011-12-21 | E-GEOD-27859 | biostudies-arrayexpress
Project description:The mononuclear phagocyte (MP) system consists of macrophages, monocytes, and dendritic cells. MP subtypes play distinct functional roles in steady-state and inflammatory conditions. Though murine MPs are well characterized, their human homologues remain poorly understood, particularly in the lung and draining lymph nodes (LNs). Understanding these homologies, and their similarities and differences with murine MPs, is critical for identifying human genetic targets and thus developing human immunotherapies. To address this gap, we performed transcriptome-based alignment across fifteen distinct human and nine distinct murine lung and LN MPs. As controls to validate the analytical quality of cross-species pulmonary MP analysis, human blood and murine spleen MPs were used. Constrained canonical correlation, t-SNE and catplot visualization was used to align human and mouse MPs and identify MP subtypes with maximal correspondence across species. Among the top marker genes expressed in corresponding human-mouse MP pairs, only 30-10% of the genes overlapped, indicating a need for caution when identifying human gene variants and functions from mice. For instance, SPP1 is highly expressed in human interstitial macrophages but not alveolar macrophages (AMs), whereas in mice SSP1 is only expressed in AMs. Moreover, human LN dendritic cells (DCs) align best with murine LN DCs but not murine splenic DCs indicating cross-species similarity in tissue. Lastly, in both species, CD88 was the most useful cell surface marker for distinguishing monocyte/macrophages from DCs. Overall, these data provide a reference for analyzing cross-species transcriptome data and evaluating whether specific murine genes are suitable guides to identify the functionality of human MPs, or conversely, whether pursuing specific human genes in mice, is likely to be a valid and fruitful approach.
2019-06-19 | GSE132911 | GEO
Project description:To determine the effect of the deletion of the trancriptional repressor Hypermethylated in cancer 1 (Hic1) on quiescence, adult mesenchymal progenitors (MPs) were isolated from skeletal muscle of both wild type mice and those conditionally deleted for Hic1 and profiled by RNA sequencing. Comparison to MPs activated by using a muscle injury model of the tibialis anterior muscle revealed similar pathways affected under both conditions, highlighting the role for Hic1 in maintaining the quiescent state of MPs
2019-12-05 | GSE110012 | GEO
Project description:In the epididymis, prevention of autoimmune responses against spermatozoa, while providing protection against pathogens, is important for male fertility. We previously showed that immune cells known as mononuclear phagocytes (MPs) are located either in the epididymal interstitium or in close proximity to the epithelium. In the initial segments (IS), these “intraepithelial” MPs extend slender luminal-reaching projections between epithelial cells. In this study, we performed an in-depth characterization of MPs isolated from IS, caput-corpus, and cauda epididymis of CX3CR1EGFP+/- mice that express EGFP in these cells. Flow cytometry analysis revealed region-specific subsets of MPs that express combinations of markers traditionally described in ‘dendritic cells’ or ‘macrophages’. RNA sequencing identified distinct transcriptomic signatures in MPs from each region, and revealed specific genes involved in inflammatory and anti-inflammatory responses, phagosomal activity, and antigen processing and presentation. Functional fluorescent in vivo labeling assays showed that higher percentages of CX3CR1+ MPs that captured and processed antigens were detected in the IS compared to other regions. Confocal microscopy showed that in the IS and corpus, circulatory antigens were internalized and processed by interstitial and intraepithelial MPs. However, in the cauda only interstitial MPs internalized and processed antigens, while intraepithelial MPs did not take up antigens, indicating that all antigens have been captured before they reached the epithelial lining. Cauda MPs may thus confer a stronger protection against blood-born pathogens compared to proximal regions. By identifying immunoregulatory mechanisms in the epididymis, our study may lead to new therapies for common disorders such as male infertility and epididymitis, and identify potential targets for immuno-contraception.
2020-02-29 | GSE136442 | GEO