Ontology highlight
ABSTRACT:
PROVIDER: PRJNA660772 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Immunosuppressive microenvironments block the activity of tumoricidal T and NK cells, allowing cancers to avoid immune elimination. Monocytic myeloid-derived suppressor cells (mMDSC) are an important component of these immunosuppressive milieus. Human mMDSC respond to stimulation via their Toll-like receptors by differentiating into macrophage. Agonists targeting TLRs 1/2 (such as PAM3) induce mMDSC to mature into immumosuppressive M2-like macrophage through a process that involves TNF and IL6. Agonists targeting TLRs 7/8 (such as R848) cause the same precursors to mature into tumoricidal M1-like macrophages, a process in which IL12 plays a central role. The immune suppression mediated by mMDSC is reversed by exposure to TLR 7/8 agonists which thus might be useful adjuncts for tumor immunotherapy. In this study we looked at several time points. hMDSC from four different donors were sorted from PBMC then cultured in the presence of R848, Pam 3 or left unstimulated for 30, 75 and 225 minutes. Late time points included samples from seven donors after 3 days in culture with the same TLR ligands. For microarray experiments total RNA was extracted, amplified into aRNA and coupled to Cy5. Similarly amplified RNA from universal RNA was coupled to Cy3 and used as a reference for each array.
2014-07-21 | E-GEOD-57032 | biostudies-arrayexpress
Project description:T cells activated in the presence or absence of TLR agonists
| PRJNA432950 | ENA
Project description:We report the gene expression differences between OT-1 T cells activated alone or in the presence of TLR1/2 (Pam3CSK4) or TLR7 (Gardiquimod). By activating OT-1 splenocytes in the presence or absence of the TLR agonists, isolating RNA from purified CD8+ T cells we show that cells activated in the presence of either TLR1/2 or TLR7 agonists had similar transcriptional profiles demonstrating an increase in Th1 cytokine expression over cells that were activated alone. This study provides a key piece of information for those designing T cell mediated therapies.
2018-12-26 | GSE110144 | GEO
Project description:Immunosuppressive microenvironments block the activity of tumoricidal T and NK cells, allowing cancers to avoid immune elimination. Monocytic myeloid-derived suppressor cells (mMDSC) are an important component of these immunosuppressive milieus. Human mMDSC respond to stimulation via their Toll-like receptors by differentiating into macrophage. Agonists targeting TLRs 1/2 (such as PAM3) induce mMDSC to mature into immumosuppressive M2-like macrophage through a process that involves TNF and IL6. Agonists targeting TLRs 7/8 (such as R848) cause the same precursors to mature into tumoricidal M1-like macrophages, a process in which IL12 plays a central role. The immune suppression mediated by mMDSC is reversed by exposure to TLR 7/8 agonists which thus might be useful adjuncts for tumor immunotherapy.
2014-07-21 | GSE57032 | GEO
Project description:Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1). Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection. To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK), and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR) pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1b, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication. HIV-1 induced a primed, proinflammatory state, M1HIV, which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic approaches. Affymetrix arrays were used to identify genomic macrophage response to HIV during viral spread in culture. Experiment Overall Design: An HIV-1 spreading infection was established in primary human macrophages. RNA was extracted from both viral- and mock-infected macrophages cultures over 7 days and hybridized to Affymetrix HG-U95Av2 GeneChips for analysis.
2009-01-15 | E-GEOD-13395 | biostudies-arrayexpress
Project description:Analysis of monocyte-derived dendritic cells (MoDC) gene expression signature induced by TLR agonists the in presence or in the absence of PP2.
2010-06-18 | E-TABM-1018 | biostudies-arrayexpress
Project description:Primary objectives: Characterization of the macrophage population subset that is modulated by enteric neurons
Primary endpoints: Characterization of the macrophage population subset that is modulated by enteric neurons via RNA sequencing
| 2538227 | ecrin-mdr-crc
Project description:Host macrophage transcriptional responses to intracellular pathogens remain poorly characterized. We screened transcriptional enhancers engaged in response to M. tuberculosis (Mtb) infection by ChIPseq analysis of histone H3 lysine 4 monomethylation (H3K4me1). De novo monomethylation during infection was associated with genes implicated in host defense and apoptosis. These regions were enriched for binding sites for ETS transcription factor family members and response elements for nuclear receptors, including liver X receptors (LXRs) and peroxisomal proliferator activated receptors (PPARs), many of which were encompassed by transposable elements. LXRa expression was strongly induced by infection, whereas that of PPARs was unaffected. LXR DNA binding and NCoR corepressor recruitment increased proportionately in infected cells but coactivator association was unchanged, consistent with a lack of induction of endogenous agonists. However, treatment of infected cells with LXR agonist T0901317 strongly increased coactivator recruitment and induced a gene expression program characterized by enhanced innate immune signaling and lipid metabolism. Remarkably, T0901317 treatment selectively induced apoptosis in infected macrophages, and was accompanied by Mtb death, reducing mycobacterial burden 18-fold relative to vehicle 5d after infection. These studies define macrophage transcriptional responses to Mtb infection, and suggest that tissue-specific LXRa agonists may be efficacious in clinical management of tuberculosis.
2015-10-15 | E-MTAB-3192 | biostudies-arrayexpress