Human Keratinocyte Response to Superantigens
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE155775 | GEO | 2020/10/01
REPOSITORIES: GEO
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Project description:The species Staphylococcus (S.) aureus harbors 19 superantigen gene loci, six of which are located in the enterotoxin gene cluster (egc). While these egc superantigens are far more prevalent in clinical S. aureus isolates than non-egc superantigens, they are not a prominent cause of toxic shock. Moreover, neutralizing antibodies against egc superantigens are very rare, even among carriers of egc-positive S. aureus strains. In search of an explanation we have tested two non-exclusive hypotheses: 1) egc and non-egc superantigens have unique intrinsic properties and drive the immune system into different directions; 2) egc and non-egc-superantigens are released by S. aureus under different conditions, which shape the immune response. A comparison of three egc (SEI, SElM and SElO) and three non-egc superantigens (SEB, SElQ, TSST-1) revealed that both induced proliferation of human PBMC with comparable potency and elicited similar Th1/Th2-cytokine signatures. This was supported by gene expression analysis of PBMC stimulated with one representative superantigen from each group (SEI and SEB). They induced very similar transcriptional changes, especially of inflammation-associated gene networks, corresponding to a very strong Th1- and Th17-dominated immune response. In contrast, the regulation of superantigen release differed markedly between both superantigen groups. Egc-encoded proteins were secreted by S. aureus during exponential growth, while non-egc superantigens were released in the stationary phase. We conclude that the distinct biological behavior of egc and non-egc superantigens is not due to their intrinsic properties, which are very similar, but caused by their differential release by S. aureus. Experiment Overall Design: PBMCs from 3 healthy blood donors were purified and treated with Medium (control) and recombinant staphylococcal superantigens SEB and SEI. After 6 hours of treatment, total RNA was extracted and hybridized to Affymetrix GeneChip Arrays.
2008-10-26 | E-GEOD-11281 | biostudies-arrayexpress
Project description:The species Staphylococcus (S.) aureus harbors 19 superantigen gene loci, six of which are located in the enterotoxin gene cluster (egc). While these egc superantigens are far more prevalent in clinical S. aureus isolates than non-egc superantigens, they are not a prominent cause of toxic shock. Moreover, neutralizing antibodies against egc superantigens are very rare, even among carriers of egc-positive S. aureus strains. In search of an explanation we have tested two non-exclusive hypotheses: 1) egc and non-egc superantigens have unique intrinsic properties and drive the immune system into different directions; 2) egc and non-egc-superantigens are released by S. aureus under different conditions, which shape the immune response. A comparison of three egc (SEI, SElM and SElO) and three non-egc superantigens (SEB, SElQ, TSST-1) revealed that both induced proliferation of human PBMC with comparable potency and elicited similar Th1/Th2-cytokine signatures. This was supported by gene expression analysis of PBMC stimulated with one representative superantigen from each group (SEI and SEB). They induced very similar transcriptional changes, especially of inflammation-associated gene networks, corresponding to a very strong Th1- and Th17-dominated immune response. In contrast, the regulation of superantigen release differed markedly between both superantigen groups. Egc-encoded proteins were secreted by S. aureus during exponential growth, while non-egc superantigens were released in the stationary phase. We conclude that the distinct biological behavior of egc and non-egc superantigens is not due to their intrinsic properties, which are very similar, but caused by their differential release by S. aureus.
2008-10-01 | GSE11281 | GEO
Project description:Staphylococcus aureus, a gram-positive bacterium, causes food poisoning and toxic shock syndrome through the production of superantigenic toxins known as Staphylococcal enterotoxins serotypes A-J (SEA, SEB, etc.) and toxic shock syndrome toxin-1 (TSST-1). A subset of these toxins have been classified as potential biothreat agents. The chronology of molecular events that could potentially characterize superantigenic toxicity and early pathogenesis is not well understood. The focus of this study was to determine the distinct and shared mechanisms of response to three toxins of the superantigenic family, namely SEA, SEB and TSST-1. Since skin functions as the front line of the host’s defense mechanism, melanocytes were selected for the study and treated with 25 µg/mL of one of these three toxins. Cells were collected after treatment for six different time periods, ranging from 0.5 h to 48 h. Total RNA was investigated using gene expression microarrays containing approximately 50,000 probes, and a subset of the results were validated using NanoString assays. Transcriptomic expression data indicated that each of these three toxins had a unique longitudinal trajectory. In particular, the gene expression profiles of SEB post-exposure was very distinct from those for SEA and TSST-1 superantigens. All three superantigens showed enriched biological networks related to necrosis, skin disorders, and inflammation. The three superantigens share some similarities in acting on the mechanisms underlying apoptosis, innate immunity, and other biological processes. Pathways related to innate immunity, such as the patterns of cytokine production and acute-phase response, showed toxin-specific regulation. The differentially regulated networks can be logical targets for early therapeutic intervention and can potentially serve as early diagnostic markers for superantigen-induced toxicity.
2022-06-30 | GSE124756 | GEO
Project description:Toxic shock syndrome (TSS) is an acute, serious systemic illness caused by bacterial superantigens (BSAg). We characterized the early molecular events underlying TSS using our HLA-DR3 transgenic mouse model and studied gene expression profiling using DNA microarrays. HLA-DR3 transgenic mice were intraperitoneally treated with either PBS or bortezomib on days -1 and 0. On day 0, each treatment group was further divided in to two groups, one received 10 μg of endotoxin-reduced highly purified SEB and the other PBS alone thus making a total of 4 groups (i.e., PBS+PBS, bortezomib+PBS, PBS+SEB, bortezomib+SEB). Three hours later, mice were euthanized by CO2 asphyxiation, spleens were immediately collected and frozen in liquid nitrogen. Once all the animals had been sacrificed, total RNA from spleens was extracted
2010-03-04 | E-GEOD-15571 | biostudies-arrayexpress
Project description:Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) was investigated in six tissues (PBMC, lung, spleen, kidney, heart, Liver).The earliest responses and largest number of affected genes occurred in tissues (PBMCs, spleen and lung) with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Global gene-expression changes measured serially across multiple organs identified new candidate mechanisms of SEB-induced death.
2014-03-01 | GSE52474 | GEO
Project description:Human Keratinocyte Response to Superantigens
| PRJNA655554 | ENA
Project description:Expression data from human PBMCs treated for 6h with the staphylococcal superantigens SEB and SEI
| PRJNA106687 | ENA
Project description:Bacterial superantigens are virulence factors that cause toxic shock syndrome. Here, the genome-wide, temporal response of mice to lethal intranasal staphylococcal enterotoxin B (SEB) was investigated in six tissues (PBMC, lung, spleen, kidney, heart, Liver).The earliest responses and largest number of affected genes occurred in tissues (PBMCs, spleen and lung) with the highest content of both T-cells and monocyte/macrophages, the direct cellular targets of SEB. In contrast, the response of liver, kidney and heart was delayed and involved fewer genes, but revealed a dominant genetic program that was seen in all 6 tissues. Many of the 85 uniquely annotated transcripts participating in this shared genomic response have not been previously linked to SEB. Global gene-expression changes measured serially across multiple organs identified new candidate mechanisms of SEB-induced death. Toxin or saline (control) was administered to male C3H/HeJ mice in 5 independent experiments. Toxin or saline was administered i.n. followed by an i.p dose two hours later. Lung, liver, heart, spleen and kidney were harvest and preserved for tRNA purification at each time point. Each PBMC sample corresponded to a pooled sample (10 mice per time point). Samples from control animals were collected at time 0, 2.75 h, 5 h and 24 h. Samples from SEB treatment were collected at 0h, 2.75h, 5 h and 24 h. Only 4 set of samples per tissue type were used for microarray.
2014-03-01 | E-GEOD-52474 | biostudies-arrayexpress
Project description:To determine how KLK5 and KLK7 can impact keratinocyte responses we treated human primary keratinocytes with recombinant KLK5 and KLK7 for 4 hours.
2023-03-01 | GSE205531 | GEO
Project description:We performed comprehensive proteome profiling (ECM and cell lysate) of human collagen VII deficient and control epidermal keratinocytes to generate global and detailed images of dysregulated epidermal molecular pathways linked to loss of collagen VII. These revealed downregulation of interaction partners of collagen VII, but also increased abundance of S100 pro-inflammatory proteins and enhanced activity of lysosomal proteases. Thus, loss of a single extracellular structural protein, collagen VII, induced persistent fibrosis enabling inflammatory and tissue destabilizing activities of keratinocytes.
2018-01-16 | PXD005873 | Pride