Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA264572 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The innate immune system is the organism’s first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level.
2017-06-12 | GSE85448 | GEO
Project description:The innate immune system acts as the first line of defense against invasion of microbial pathogens. Here, macrophages play a substantial role in recognition, phagocytosis and killing of pathogens and the regulation of the innate immune response. Here, interferons play a crucial role in augmenting the antimicrobial functions of macrophages and their ability to produce mediators of immunoregulation. Pathogen recognition activates many different signaling pathways that interact to produce an innate response commensurate with the microbial challenge. The co-occurrence of signaling by sensors of stress and IFN receptors is a hallmark of innate responses to many viral and bacterial pathogens. Our results show how Anisomycin, a drug that induces stress-activation of MAPK pathways, regulates mRNA expression of interferon stimulated genes (ISG) upon IFNg and IFNb stimulation
2022-12-18 | GSE199128 | GEO
Project description:The innate immune system acts as the first line of defense against invasion of microbial pathogens. Here, macrophages play a substantial role in recognition, phagocytosis and killing of pathogens and the regulation of the innate immune response. Here, interferons play a crucial role in augmenting the antimicrobial functions of macrophages and their ability to produce mediators of immunoregulation. Pathogen recognition activates many different signaling pathways that interact to produce an innate response commensurate with the microbial challenge. The co-occurrence of signaling by sensors of stress and IFN receptors is a hallmark of innate responses to many viral and bacterial pathogens. Our results show changes in chromatin accessibility upon Anisomycin, a drug that induces stress-activation of MAPK pathways, IFNg stimulation and the combination of both or with p38 inhibitor PH-797804, Anisomycin and IFNg.
2022-12-18 | GSE199126 | GEO
Project description:The innate immune system acts as the first line of defense against invasion of microbial pathogens. Here, macrophages play a substantial role in recognition, phagocytosis and killing of pathogens and the regulation of the innate immune response. Here, interferons play a crucial role in augmenting the antimicrobial functions of macrophages and their ability to produce mediators of immunoregulation. Pathogen recognition activates many different signaling pathways that interact to produce an innate response commensurate with the microbial challenge. The co-occurrence of signaling by sensors of stress and IFN receptors is a hallmark of innate responses to many viral and bacterial pathogens. Our results show changes in chromatin accessibility upon Anisomycin, a drug that induces stress-activation of MAPK pathways, IFNb stimulation and the combination of both or with p38 inhibitor PH-797804, Anisomycin and IFNb.
2022-12-18 | GSE199125 | GEO
Project description:The innate immune system acts as the first line of defense against invasion of microbial pathogens. Here, macrophages play a substantial role in recognition, phagocytosis and killing of pathogens and the regulation of the innate immune response. Here, interferons play a crucial role in augmenting the antimicrobial functions of macrophages and their ability to produce mediators of immunoregulation. Pathogen recognition activates many different signaling pathways that interact to produce an innate response commensurate with the microbial challenge. The co-occurrence of signaling by sensors of stress and IFN receptors is a hallmark of innate responses to many viral and bacterial pathogens. Our results show c-Jun and CREB binding upon Anisomycin, a drug that induces stress-activation of MAPK pathways, IFNg stimulation and the combination of both or with p38 inhibitor PH-797804 and JNK inhibitor SP600125, Anisomycin and IFNg.
2022-12-18 | GSE199127 | GEO
Project description:Cutaneous lupus erythematosus (CLE) is a photosensitive autoimmune disease characterized by a strong type-I-interferon (IFN) associated inflammation. Keratinocytes are known to determine the interface-dermatitis-pattern in CLE by production of proinflammatory cytokines in the lower epidermis. These cytokines drive a cytotoxic anti-epithelial immune response resulting in keratinocytic cell death and release of endogenous nucleic acids (eNA). We hypothesized that these eNA (RNA- and DNA-motifs) have the capacity to activate innate immune pathways in keratinocytes via pathogen-recognition-receptors (PRR). Gene expression analyses revealed an excessive activation of innate immune response pathways with strong expression of IFN-regulated cytokines in CLE skin lesions. Cultured keratinocytes produce large amounts of these cytokines in response to stimulation of PRR with eNA. UV-stimulation enhances the immunogenicity of eNA and induces CLE-like skin lesions in knockout mice lacking the cytosolic DNase TREX1. Our results provide evidence for a pathogenetic role of endogenous nucleic acids in CLE. They are released within the cytotoxic inflammation along the dermo-epidermal junction and have the capacity to drive the LE-typical inflammation. UV-irradiation supports this inflammation by generation of highly immunostimulatory DNA motifs (8-OHG). These findings explain the photosensitivity of lupus patients and identify pathways of the innate immune system as targets for future therapies.
2017-03-01 | GSE95474 | GEO
Project description:The innate immune system is the organism’s first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level. In addition to forming macrophages and dendritic cells, monocytes in adult peripheral blood retain the ability to develop into osteoclasts, mature bone-resorbing cells. The extensive morphological and functional transformations that occur during osteoclast differentiation require substantial reprogramming of gene and protein expression. Here we employ -omic-scale technologies to examine in detail the molecular changes at discrete developmental stages in this process (precursor cells, intermediate osteoclasts, and multinuclear osteoclasts), quantitatively comparing their transcriptomes and proteomes.
2016-10-12 | GSE87805 | GEO
Project description:Germline-encoded pattern recognition receptors (e.g. Toll-like receptors) play key roles in innate immune activation. However, some metazoans, such as C. elegans, do not have canonical mechanisms of pattern recognition, yet they are able to mount anti-pathogen immune defenses. Here, we demonstrate that a nuclear hormone receptor (NHR), a ligand-gated transcription factor, functions in immune activation and pathogen defense. NHRs have expanded dramatically in C. elegans compared to other metazoans. Because NHRs often function redundantly, it has been challenging experimentally to characterize the biology of individual NHRs. Here, we use genetic epistasis experiments, transcriptome profiling analyses and chromatin immunoprecipitation to show NHR-86 is sufficient to activate protective immune defenses against the bacterial pathogen Pseudomonas aeruginosa. Interestingly, NHR-86 drives the transcription of immune effectors whose basal regulation requires the canonical p38 MAPK PMK-1 immune pathway. However, NHR-86 functions independently of PMK-1 and directly induces the transcription of infection response genes in a manner that confers protection from bacterial infection. Importantly, we found that nhr-86 does control immune gene expression and is necessary for host defense against a different pathogen, Enterococcus faecalis. Our findings characterize an ancient role of an NHR in innate immunity, and suggest that the expansion of the NHR protein family in C. elegans has been fueled in part by the need to activate immune defenses in response to pathogen attack.
2019-01-09 | GSE117700 | GEO
Project description:Germline-encoded pattern recognition receptors (e.g. Toll-like receptors) play key roles in innate immune activation. However, some metazoans, such as C. elegans, do not have canonical mechanisms of pattern recognition, yet they are able to mount anti-pathogen immune defenses. Here, we demonstrate that a nuclear hormone receptor (NHR), a ligand-gated transcription factor, functions in immune activation and pathogen defense. NHRs have expanded dramatically in C. elegans compared to other metazoans. Because NHRs often function redundantly, it has been challenging experimentally to characterize the biology of individual NHRs. Here, we use genetic epistasis experiments, transcriptome profiling analyses and chromatin immunoprecipitation to show NHR-86 is sufficient to activate protective immune defenses against the bacterial pathogen Pseudomonas aeruginosa. Interestingly, NHR-86 drives the transcription of immune effectors whose basal regulation requires the canonical p38 MAPK PMK-1 immune pathway. However, NHR-86 functions independently of PMK-1 and directly induces the transcription of infection response genes in a manner that confers protection from bacterial infection. Importantly, we found that nhr-86 does control immune gene expression and is necessary for host defense against a different pathogen, Enterococcus faecalis. Our findings characterize an ancient role of an NHR in innate immunity, and suggest that the expansion of the NHR protein family in C. elegans has been fueled in part by the need to activate immune defenses in response to pathogen attack.
2019-01-09 | GSE117719 | GEO
Project description:Pattern recognition of bacterial products by host receptors is essential for pathogen sensing in many metazoans. Caenorhabditis elegans, however, do not utilize canonical pattern recognition receptors to activate innate immunity toward bacterial pathogens. Whether other mechanisms evolved in nematodes to directly sense pathogens is not known. Here, we characterize the first bacterial pattern recognition receptor and its natural ligand in C. elegans. We show that the C. elegans nuclear hormone receptor NHR-86/HNF4 senses phenazine-1-carboxamide (PCN), a metabolite produced by pathogenic strains of Pseudomonas aeruginosa, to activate protective anti-pathogen defenses in the intestine. PCN binds to the ligand binding domain of NHR-86/HNF4, a ligand-gated transcription factor, which engages a transcriptional program in intestinal epithelial cells that promotes metabolism of toxic phenazines to provide protection against P. aeruginosa. These data de-orphan a nuclear hormone receptor and demonstrate that sensing a metabolite signal of bacterial virulence allows nematodes to detect pathogens in its environment that are poised to cause disease.
2023-02-07 | GSE202258 | GEO