Pycnogenol
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB29793 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR2915201_1.fastq.gz | Fastqsanger.gz | |||
| ERR2915201_2.fastq.gz | Fastqsanger.gz | |||
| ERR2915202_1.fastq.gz | Fastqsanger.gz | |||
| ERR2915202_2.fastq.gz | Fastqsanger.gz | |||
| ERR2915203_1.fastq.gz | Fastqsanger.gz |
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Project description:Multiple studies have established associations between human gut bacteria and host physiology but determining the molecular mechanisms underlying these associations has been challenging1–3. Akkermansia muciniphila has been robustly associated with positive systemic effects on host metabolism, favorable outcomes to checkpoint blockade in cancer immunotherapy, and homeostatic immunity4–7. Here we report the identification of a lipid from A. muciniphila’s cell membrane that recapitulates the immunomodulatory activity of A. muciniphila in cell-based assays8. The isolated immunogen, a diacyl phosphatidylethanolamine with two branched chains (a15:0-i15:0 PE), was characterized through both spectroscopic analysis and chemical synthesis. The immunogenic activity of a15:0-i15:0 PE has a highly restricted structure-activity relationship, and its immune signaling requires an unexpected toll-like receptor 2/1 heterodimer9,10. Certain features of the phospholipid’s activity are noteworthy: it is significantly less potent than known natural and synthetic toll-like receptor 2 agonists; it preferentially induces some inflammatory cytokines but not others; and at low doses (1% of EC50) it resets activation thresholds and responses for immune signaling. Identifying both the molecule and an equipotent synthetic analog, its non-canonical toll-like receptor 2/1 signaling pathway, its immunomodulatory selectivity, and its low dose immunoregulatory effects provides a molecular mechanism for a model of A. muciniphila’s ability to set immunological tone and its varied roles in health and disease.
2022-07-10 | GSE199367 | GEO
Project description:Nanomaterials offer new opportunities to engineer immunomodulatory activity. In this work, we report the endosomal toll-like receptor agonist activity of a nanoscale adjuvant zeolitic imidazolate frameworks-8 (ZIF-8). The accumulation of ZIF-8 in endosomes and the pH-responsive release of its subunits enable selective engagement with endosomal TLRs, minimizing the risk of off-target activation. The intrinsic adjuvant properties of ZIF-8, along with the efficient delivery and biomimetic presentation of a SARS-CoV-2 spike protein receptor binding domain trimer, primed rapid humoral and cell mediated immunity in a dose sparing manner. Our study offers new insights for next-generation adjuvants that can potentially impact future vaccine development.
2024-03-13 | GSE246178 | GEO
Project description:Talactoferrin alfa (TLF) is a unique recombinant version of human lactoferrin, an important immunomodulatory protein present in exocrine secretions and in the secondary granules of neutrophils. Talactoferrin has demonstrated anti-cancer activity in preclinical studies and in Phase III clinical trials in patients with Renal Cell Cancer and non-small cell lung cancer. We have shown that TLF induces the maturation of human DCs derived from monocytes, suggesting that the linkage of the innate and adaptive immunity through DC maturation is a key immune function mediated by TLF. In this study we used genome-wide expression analysis to explore the mechanisms by which TLF leads to the functional maturation of DC. We show that GMP level recombinant TLF activates human DCs in a Toll-like receptor (TLR) -2 and -4 dependent manner.
2013-12-30 | GSE26438 | GEO
Project description:We report the application of bulk RNA sequencing for profiling changes in mouse cardiac lysates as a result of changes in innate immunity function. We generated an inducible endothelial cell toll-like receptor 2 knockout and assessed changes in overall gene expression in the absence of pathogen presence. We find that over 200 genes are differentially regulated between the two genotypes that are solely due to the presence of endogenous signaling within these animals. We also show that the genes that are differentially regulated are tied to the immunity function of the endothelium and that removal of toll-like receptor 2 signaling creates a diminished response by the immune system to wound healing and tumor development. Finally, we demonstrate that other immunomodulatory pathways are further affected, suggesting that changes outside of the endothelium are driven by endothelial-toll-like receptor 2 signaling. This study provides a framework for the application of tissue specific knockouts and profiling the role of endothelial as an innate immunity organ.
2021-05-19 | GSE155090 | GEO
Project description:Talactoferrin alfa (TLF) is a unique recombinant version of human lactoferrin, an important immunomodulatory protein present in exocrine secretions and in the secondary granules of neutrophils. Talactoferrin has demonstrated anti-cancer activity in preclinical studies and in Phase III clinical trials in patients with Renal Cell Cancer and non-small cell lung cancer. We have shown that TLF induces the maturation of human DCs derived from monocytes, suggesting that the linkage of the innate and adaptive immunity through DC maturation is a key immune function mediated by TLF. In this study we used genome-wide expression analysis to explore the mechanisms by which TLF leads to the functional maturation of DC. We show that GMP level recombinant TLF activates human DCs in a Toll-like receptor (TLR) -2 and -4 dependent manner. Human peripheral blood mononuclear cells (PBMCs) were obtained from buffy coats of healthy donors. CD14+ cells were isolated from fresh PBMCs by positive immunoselection with magnetic beads. Immature dendritic cells (i-DC) from four donors were generated using granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4. On day 6, cells were harvested in order to have iDC or mDC (conventionally matured DC) by addition of Tumor Necrosis Factor (TNF) -alfa and IL-1beta or TLF-DC (Talactoferrin matured DC) adding Food and Drug Administration-approved, GMP level recombinant TLF generated in eukaryotic cells. After 24 hour culture, cells were harvested and analyzed with Illumina arrays.
2013-12-30 | E-GEOD-26438 | biostudies-arrayexpress
Project description:We aimed to determine the relative contributions of MyD88- and TRIF-dependent signaling in Toll-like receptor-induced trained immunity in macrophages.
2022-10-28 | GSE205186 | GEO
Project description:The noncanonical inflammasome induced by intracellular lipopolysaccharide (LPS) leads to caspase-11-dependent pyroptosis, which is critical for induction of endotoxic shock in mice. However, the signaling pathway downstream of caspase-11 is unknown. We found that cytosolic LPS stimulation induced caspase-11-dependent cleavage of the pannexin-1 channel followed up by ATP release, which in turn activated the purinergic P2X7 receptor to mediate cytotoxicity. In the absence of P2X7 or pannexin-1, pyroptosis induced by cytosolic LPS was abrogated. Cleavage of pannexin-1 required the catalytic activity of caspase-11 and was essential for ATP release and P2X7-mediated pyroptosis. Priming the caspase-11 pathway in vivo with LPS or Toll-like receptor-3 (TLR3) agonist resulted in high mortality in wild-type mice after secondary LPS challenge, but not in Casp11(-/-), Panx1(-/-), or P2x7(-/-) mice. These results reveal a critical role for pannexin-1 and P2X7 downstream of caspase-11 for pyroptosis and susceptibility to sepsis induced by the noncanonical inflammasome.
Research is published, core data not used but project description is relevant:
http://www.sciencedirect.com/science/article/pii/S1074761315004094
2015-06-05 | ST000174 | MetabolomicsWorkbench
Project description:Hyriopsis cumingii Toll-like receptor 1
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Project description:Tissue morphogenesis requires the spatial control over actomyosin contractility to drive cell shape changes. How developmental patterning information controls cell mechanics is poorly understood. In the Drosophila embryo ectoderm, Myosin-II is enriched at the interface between antero-posterior neighboring cells, leading to planar polarized cell intercalation. G protein-coupled receptors (GPCRs) are required for planar polarized Myosin-II activation at junctions and Toll receptors provide a positional code underlying this process. How Toll receptors polarize actomyosin contractility remains unknown. Here we report that cells expressing different levels of a single Toll receptor Toll-8 activate Myosin-II at their interface. Surprisingly, the Toll-8 intracellular domain is not required for signaling at cell interfaces suggesting signaling by proxy. We found that Toll-8 forms a molecular complex with the adhesion GPCR Cirl/Latrophilin that is required for Toll-8 dependent junctional Myosin-II activation. Strikingly, the interfaces between Cirl expressing and cirl mutant cells also activate Myosin-II suggesting that Toll-8 induces Cirl asymmetric signaling at cell interfaces. We further showed that Toll-8 recruits Cirl both in trans and in cis, inducing asymmetric Cirl localization at the boundary of the Toll-8 expression domain. Finally, we found that Toll-8 and Cirl exhibit dynamic interdependent planar polarization when neighboring cells express different levels of Toll-8. Through this feedback, Toll-8 and Cirl self-organize planar polarized signaling.
2021-04-22 | PXD017895 | Pride