Monocyte exhaustion mediated by TRAM
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE182355 | GEO | 2021/10/22
REPOSITORIES: GEO
Similar Datasets
Project description:We performed scRNAseq analysis of murine monocytes cultured from bone marrow isolates of WT and TRAM knockout mice. WT and TRAM knockout monocytes were cultured in vitro for 5 days in the presence or absence of low dose LPS (100 pg/ml).
2021-11-10 | GSE182237 | GEO
Project description:Monocyte exhaustion characterized by sustained pathogenic inflammatory and immune-suppressive features underlies the pathogenesis of sepsis induced by systemic polymicrobial infections. However, effective strategies in blocking monocyte exhaustion and restoring innate homeostasis are currently not available. In this study, we found that Methoxy-Mycolic Acid (M-MA), a branched mycolic acid derived from Mycobacterium Bovis Bacillus Calmette–Guérin (BCG), to be a potent agent in alleviating monocyte exhaustion and restoring immune homeostasis. Co-treatment of monocytes with M-MA can effectively block the expansion of exhausted Ly6Chi /CD38hi/PD-L1hi monocytes induced by repetitive LPS challenges, and restore the expression of immune-enhancing CD86 on co-treated monocytes. Functionally, M-MA treatment restored mitochondrial functions of exhausted monocytes and alleviated their suppressive activities on co-cultured T cells. Mechanistically, M-MA exerts its protective effects independent of cellular receptor TREM2, and relieves cellular stress signaling through blocking Src-STAT1 mediated pathogenic inflammatory polarization as well as reducing the production of compensatory immune suppressors TAX1BP1 and PLAC8. Our whole genome methylation analyses further revealed that M-MA can effectively erase methylation memory of exhausted monocytes, with validated restoration of plac8 methylation by M-MA. Together, our data reveal M-MA as a potent agent in restoring monocyte homeostasis with future therapeutic potential for the treatment of sepsis.
2023-12-19 | GSE242825 | GEO
Project description:Chronic, low-grade inflammation has a widespread and significant impact on health, especially in Western-society. While inflammation is beneficial for the removal of microbes, low-grade inflammation never resolves and can cause or worsen other diseases. However, the process by which low-grade inflammation occurs is poorly understood. As lipopolysaccharide (LPS) is associated with chronic inflammatory diseases, we exposed murine bone-marrow derived monocytes to chronic LPS-stimulation at Low-dose (100pg/mL) or High-dose (1 µg/mL), as well as a PBS control. The cells were profiled for H3K27ac expression and gene expression. The gene expression of TRAM-deficient and IRAK-M-deficient mice with LPS exposure was also analyzed for mechanistic insight. We determined that many of the differences between the Low-dose and High-dose conditions are related to the TRIF-dependent pathway of TLR4 signaling. Furthermore, these changes are also seen in the epigenome, suggesting the epigenome may be what leads to the differential response. These findings further characterize the different means utilized in low-grade conditions, and how it might lead to a damaging, non-resolving state. Moreover, our data provide potential targets for future mechanistic or therapeutic studies.
2021-03-18 | GSE168190 | GEO
Project description:Monocyte exhaustion mediated by TRAM
| PRJNA755992 | ENA
Project description:Innate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression and emergency hematopoiesis. Epigenetic changes, notably via histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA methylation remains poorly understood. Using an ex vivo sepsis model, we discovered broad changes in DNA methylation throughout the genome of exhausted monocytes, including at several genes implicated in immune dysregulation during sepsis and Covid-19 infection (e.g. Plac8). Methylome reprogramming is driven in part by Wnt signaling inhibition in exhausted monocytes, and can be reversed with DNA methyltransferase inhibitors, Wnt agonists, or immune training molecules. These changes are recapitulated in septic mice following cecal slurry injection, supporting the involvement of DNA methylation in acute and long-term monocyte dysregulation during sepsis.
2024-03-05 | GSE242816 | GEO
Project description:Innate immune memory is the process by which pathogen exposure elicits cell-intrinsic states to alter the strength of future immune challenges. Such altered memory states drive monocyte dysregulation during sepsis, promoting pathogenic behavior characterized by pro-inflammatory, immunosuppressive gene expression and emergency hematopoiesis. Epigenetic changes, notably via histone modifications, have been shown to underlie innate immune memory, but the contribution of DNA methylation remains poorly understood. Using an ex vivo sepsis model, we discovered broad changes in DNA methylation throughout the genome of exhausted monocytes, including at several genes implicated in immune dysregulation during sepsis and Covid-19 infection (e.g. Plac8). Methylome reprogramming is driven in part by Wnt signaling inhibition in exhausted monocytes, and can be reversed with DNA methyltransferase inhibitors, Wnt agonists, or immune training molecules. These changes are recapitulated in septic mice following cecal slurry injection, supporting the involvement of DNA methylation in acute and long-term monocyte dysregulation during sepsis.
2024-03-05 | GSE253201 | GEO
Project description:We analyzed the delayed LPS-induced expression pattern in monocytes. Activation of monocytes by microbial products is an important mechanism contributing to host protection against invading pathogens. This process has to be tightly controlled to ensure that antimicrobial response does not result in fatal host tissue damage. Therefore we investigated control mechanisms during prolonged monocyte activation by bacterial endotoxin.
2015-03-06 | GSE55608 | GEO
Project description:Tumor associated macrophages and T cells were characterized in a cohort of 73 ccRCC and 5 healthy donors using mass cytometry. Macrophage and T cell subsets of interest were identified and sorted directly from samples known to contain a high frequency of these subsets. CD8+ PD-1- T cells (n=6), exhausted CD8+ PD-1+ T cells (n=6), control macrophages CD14+ HLA-DR+ CD204- CD38- CD206- (n=11) and a population of TAM characterized as CD14+ HLA-DR+ CD204+ CD38+ CD206- (n=6) were isolated using FACS sorting.
2017-05-04 | E-MTAB-5640 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to compare the mircoRNA expression profiles from monocytes challegned with subclinical low dosage of LPS Methods: Primary murine bone marrow derived monocytes treated with or without 5 pg/ml LPS in complete culture medium. Harvested mircoRNAs were used to prepare libaray for subsequent sequencing, in triplicate, using HiSeq 1000. Sequences were assayed to ensure high quality for all samples using a custom R script. Reads were first trimmed for adaptor and quality using a combination of custom perl scripts and Btrim64. After trimming, trimmed fastq sequences were imported into mirAnalyzer for mapping, miRNA assembly and prediction, quantitation and differential expression. qRT–PCR validation was performed to validate selected microRNAs. Results: miRNA-seq data confirmed selective induction of a limited set of mircoRNAs in monocytes treated with subclinical super-low dose LPS. Conclusions: Our study revealed that there are selected miroRNAs preferentially induced in monocytes challenged with subclinical low dosage of LPS.
2016-10-28 | GSE87396 | GEO
Project description:CD14+ Monocytes from healthy volunteers were purified by MACS (negative selection) and FACSorting and either left untreated or stimulated for 24h and 48h with LPS. THP-1 cells were stimulated for 4h, 24h and 48h with LPS. Glycoproteins were captured with hydrazide chemistry and tryptic and PNGase F-released peptide fractions analyzed by MS/MS. Quantitative assessment revealed differential glycoprotein expression in activated/LPS-tolerized monocytes and naïve monocytes and THP-1 cells.
2017-04-24 | PXD004034 | Pride