Transcriptome characterization of immune suppression from battlefield-like stress
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE39148 | GEO | 2014/10/27
SECONDARY ACCESSION(S): PRJNA170109
REPOSITORIES: GEO
Similar Datasets
Project description:Background: Severe stress can have drastic and systemic effects with dire implications on the health and wellbeing of exposed individuals. Particularly, the effect of stress on the immune response to infection is of interest because of its implications for vaccine efficacy and treatment strategy during stressful scenarios. Battlefield-like stress has previously been shown to cause an anergic state in the immune system that persists following exposure to a potent mitogen. Methods: Genome-wide alterations of gene expression were characterized using leukocytes collected from (15 informed and consented, all male) U.S. Army Ranger cadets immediately before and after training followed by exposure to a representative group of pathogens Yersinia pestis, dengue virus, Staphylococcus enterotoxin B (SEB). We employed experimental and computational approaches in identifying altered molecules, processes, pathways, and functional and regulatory networks mediating the host’s response towards battlefield-like stress, in assessing protective immunity status of the stressed host towards infection, and in identifying pathogen-induced biomarkers under severe stress background. Results: We observed predicted inhibition of pathways significantly associated with lymphopoiesis, wound healing, inflammatory response, lymphocyte activation, apoptosis, and predicted activation of oxidative stress. Using weighted correlation network analyses, we showed preservation of these pathways across infection plus stress combinations. Regulatory networks comprising a common set of upstream regulators: transcription factors, microRNAs and post-translational regulators (kinases, phosphatases) may be drivers of molecular alterations leading compromised protective immunity. Other sets of transcripts were persistently altered in both the pre- and post-stress conditions due to the host’s response to each pathogen forming pathogen-specific molecular signatures with a potential to distinguish infection from that of severe stress. Conclusion: Our results suggest that severe battlefield-like stress alters molecular players implicated in the developments of hematopoietic stem cells probably leading to depletion of cellular and molecular repertoires of protective immunity, membrane trafficking of recycling endosomes and membrane translocation of the antigen processing mechanisms leading to suboptimal antigen processing and presentation, cell adhesion leading to impaired formation of productive immunological synapse, and inhibited T-cell activation. These factors may collectively be responsible for compromised protective immunity (infection susceptibility, delayed wound healing and poor vaccine response), and cellular anergy.
2021-07-05 | GSE117464 | GEO
Project description:Genome-wide alterations of gene expression were characterized using leukocytes collected from (informed and consented, all male) U.S. Army Ranger cadets immediately before and after training followed by exposure to a representative group of pathogens Yersinia pestis, dengue virus, Staphylococcus enterotoxin B. We employed experimental and computational approaches in identifying altered molecules, processes, pathways, and functional and regulatory networks mediating the host’s response towards battlefield-like stress, in assessing protective immunity status of the stressed host towards infection, and in identifying pathogen-induced biomarkers under severe stress background. We observed predicted inhibition of pathways significantly associated with lymphopoiesis, wound healing, inflammatory response, lymphocyte activation, apoptosis, and predicted activation of oxidative stress. Using weighted correlation network analyses, we showed preservation of these pathways across infection plus stress combinations. Regulatory networks comprising a common set of upstream regulators: transcription factors, microRNAs and post-translational regulators (kinases, phosphatases) may be drivers of molecular alterations leading compromised protective immunity. Other sets of transcripts were persistently altered in both the pre- and post-stress conditions due to the host’s response to each pathogen forming pathogen-specific molecular signatures with a potential to distinguish infection from that of severe stress. Our results suggest that severe battlefield-like stress alters molecular players implicated in the developments of hematopoietic stem cells probably leading to depletion of cellular and molecular repertoires of protective immunity, membrane trafficking of recycling endosomes and membrane translocation of the antigen processing mechanisms leading to suboptimal antigen processing and presentation, cell adhesion leading to impaired formation of productive immunological synapse, and inhibited T-cell activation. These factors may collectively be responsible for compromised protective immunity (infection susceptibility, delayed wound healing and poor vaccine response), and cellular anergy.
2021-07-05 | GSE116725 | GEO
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: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:R. conorii transcriptional response within inoculation eschar battlefield
| PRJNA113491 | ENA
Project description:Purpose: The goal of this study was to determine what genes and canonical pathways are altered by exposure of human keratinocytes to S. aureus superantigens TSST-1 or SEB; Methods: Primary human keratinocytes were treated with 100 ug purified TSST-1, SEB, or vehicle for 6 hours. RNA was extracted with Trizol, DNase treated, and purifed using a Qiagen column. RNAseq was used to assess gene expression. Bioinformatic analyses were used to determing differential gene expression between superantigen treated cells and controls. Validition of cytokine increases was performed using ELISAs.
2020-10-01 | GSE155775 | GEO
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:Gene Expression Changes Induced by Bacterial Superantigen, Staphylococcal Enterotoxin B
| PRJNA115745 | ENA
Project description:Staphylococcus Enterotoxin B (SEB) is an exotoxin produced by Staphylococcus aureus. It is a public health threat during nosocomial infections. It is also considered as a biological weapon. The Centers for Disease Control and Prevention (CDC) lists SEB as a category B agent of Biodefence. SEB is easily aerosolized and can enter the host through inhalation which could lead to Acute Lung Injury (ALI) and in severe cases, it may result in multiple organ failure, shock and death. It is considered to be a Super-antigen as it activates a large number (30%) of T cells and results in the production of cytokines SEB binds directly to the non polymorphic region of MHC Class II which is expressed on antigen presenting cells and this complex activates T cells expressing a specific variable region of the β chain (Vβ8) of the T cell receptor (TCR). Thus, inhalation of SEB leads to recruitment of immune cells into the lung and secretion of pro-inflammatory cytokines which results in severe damage to the lung by increasing the permeability, and induction of respiratory failure. MicroRNA (miRNAs) is considered one of the mechanisms by which the epigenetic regulation happens. MicroRNA are noncoding small RNAs that have recently been shown to play a role in gene expression. The action of miRNA is dependent on its binding to 3’ Untranslated Region (3’UTR) of mRNA resulting in transcriptional or translational repression. Specifically, the efficacy of gene silencing is determined by the interaction of miRNA seed sequence with the target mRNA. Endocannabinoids are lipid molecules produced endogenously by host cells and bind to cannabinoid receptors, CB1 and CB2. N-Arachidonoylethanolamide or anandamide (AEA) is an endocannabinoid that has been shown to have immunomodulatory effects by our lab and others, although the precise mechanism is not clear. So far through my research, I found that Endocannabinoid is involved in a very unique way in the anti-inflammatory response through upregulation of many anti-inflammatory genes such as FOXP3, ARG1, and IL-10 that targeted by miRNA23a-3p and miRNA 34a-5p as well as the anti-inflammatory phenotype population as it show in the RT-PCR and flow cytometry results.
2023-05-31 | E-MTAB-10274 | biostudies-arrayexpress