Transcriptional response signature of human lymphoid cells to staphylococcal enterotoxin B

Mendis, Chanaka; Das, Rina; Hammamieh, Rasha; Royaee, Atabak R.; Yang, David C.H.; Peel, Sheila A.; Jett, Marti

doi:10.1038/sj.gene.6364160

Cited by 11 publications

(15 citation statements)

References 27 publications

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“…Stimulation with SEI and/or SEB changed the transcription of 391 genes, two thirds of which were up-regulated. This is in agreement with Mendis and coworkers (35), who also treated PBMC with SEB. Stimulation with SEI was slightly stronger than with SEB, probably because this SAg activates a larger fraction of T cells.…”

Section: Discussionsupporting

confidence: 81%

Immune Cell Activation by Enterotoxin Gene Cluster (egc)-Encoded and Non-egc Superantigens from Staphylococcus aureus

Grumann

Scharf

Holtfreter

et al. 2008

The Journal of Immunology

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The species Staphylococcus aureus harbors 19 superantigen gene loci, six of which are located in the enterotoxin gene cluster (egc). Although 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 Abs 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 and 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, and toxic shock syndrome toxin-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. The Journal of Immunology, 2008, 181: 5054 -5061. Staphylococcus aureus is both a successful colonizer and an important pathogen in humans. These bacteria cause a wide spectrum of infectious diseases including several toxin-mediated diseases. Among the numerous toxins of S. aureus are the 19 known staphylococcal superantigens (SAgs) 3 : the toxic shock syndrome toxin (TSST-1), the staphylococcal enterotoxins (SEA-SEE, SEG-SEJ), and the staphylococcal enterotoxin-like toxins (SElK-SElR and SElU) (1-4). SAgs are the causative agents of toxic shock syndrome, and might also contribute to septic shock (3, 5). They directly cross-link conserved regions of the variable domains of the TCR ␤-chain (TCR V␤) with MHC class II molecules (outside the peptide-binding cleft) on APCs. This results in a strong stimulation of T cells that express the matching TCR V␤ element on their surface. Activated T cells respond with proliferation and massive cytokine release. In this way, SAgs activate up to 20% of all T cells. In contrast, conventional Ags only stimulate around 0.001% of T cells. They require uptake by APCs, processing into peptides, loading onto MHC-II molecules, and presentation on the cell surface, where their specific recognition is mediated by the hypervariable loops of TCR ␣-and ␤-chains.The recentl...

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Section: Discussionsupporting

confidence: 81%

Immune Cell Activation by Enterotoxin Gene Cluster (egc)-Encoded and Non-egc Superantigens from Staphylococcus aureus

Grumann

Scharf

Holtfreter

et al. 2008

The Journal of Immunology

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“…Neisseria meningitidis induces more IL-10 but less IFN-␥ production than Streptococcus pneumoniae, while Staphylococcus aureus induced minimal secretion of both cytokines (4). The results of analysis of samples from patients with staphylococcal enterotoxin B-and lipopolysaccharide-induced septic shock have identified pathogen-specific genomic markers and indicates that some can also be stage specific (26). Different transcriptional programs can be triggered upon in vitro exposure of immune cells to distinct pathogens (5,9,28).…”

Section: Discussionmentioning

confidence: 93%

Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients

Lukaszewski

Yates

Jackson

et al. 2008

Clin Vaccine Immunol

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Postoperative or posttraumatic sepsis remains one of the leading causes of morbidity and mortality in hospital populations, especially in populations in intensive care units (ICUs). Central to the successful control of sepsis-associated infections is the ability to rapidly diagnose and treat disease. The ability to identify sepsis patients before they show any symptoms would have major benefits for the health care of ICU patients. For this study, 92 ICU patients who had undergone procedures that increased the risk of developing sepsis were recruited upon admission. Blood samples were taken daily until either a clinical diagnosis of sepsis was made or until the patient was discharged from the ICU. In addition to standard clinical and laboratory parameter testing, the levels of expression of interleukin-1␤ (IL-1␤), IL-6, IL-8, and IL-10, tumor necrosis factor-␣, FasL, and CCL2 mRNA were also measured by real-time reverse transcriptase PCR. The results of the analysis of the data using a nonlinear technique (neural network analysis) demonstrated discernible differences prior to the onset of overt sepsis. Neural networks using cytokine and chemokine data were able to correctly predict patient outcomes in an average of 83.09% of patient cases between 4 and 1 days before clinical diagnosis with high sensitivity and selectivity (91.43% and 80.20%, respectively). The neural network also had a predictive accuracy of 94.55% when data from 22 healthy volunteers was analyzed in conjunction with the ICU patient data. Our observations from this pilot study indicate that it may be possible to predict the onset of sepsis in a mixed patient population by using a panel of just seven biomarkers.

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“…16 Leukocytes of soldiers collected before and after RASP were challenged ex vivo with SEB, and immune response transcripts were analyzed. In pre-RASP leukocytes, SEB toxin induced a majority of immune response genes (Figure 4).…”

Section: Resultsmentioning

confidence: 99%

Transcriptome characterization of immune suppression from battlefield-like stress

et al. 2012

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Transcriptome alterations of leukocytes from soldiers who underwent 8 weeks of Army Ranger training (RASP, Ranger Assessment and Selection Program) were analyzed to evaluate impacts of battlefield-like stress on the immune response. About 1400 transcripts were differentially expressed between pre- and post-RASP leukocytes. Upon functional analysis, immune response was the most enriched biological process, and most of the transcripts associated with the immune response were downregulated. Microbial pattern recognition, chemotaxis, antigen presentation and T-cell activation were among the most downregulated immune processes. Transcription factors predicted to be stress-inhibited (IRF7, RELA, NFκB1, CREB1, IRF1 and HMGB) regulated genes involved in inflammation, maturation of dendritic cells and glucocorticoid receptor signaling. Many altered transcripts were predicted to be targets of stress-regulated microRNAs. Post-RASP leukocytes exposed ex vivo to Staphylococcal enterotoxin B showed a markedly impaired immune response to this superantigen compared with pre-RASP leukocytes, consistent with the suppression of the immune response revealed by transcriptome analyses. Our results suggest that suppression of antigen presentation and lymphocyte activation pathways, in the setting of normal blood cell counts, most likely contribute to the poor vaccine response, impaired wound healing and infection susceptibility associated with chronic intense stress.

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Transcriptional response signature of human lymphoid cells to staphylococcal enterotoxin B

Cited by 11 publications

References 27 publications

Immune Cell Activation by Enterotoxin Gene Cluster (egc)-Encoded and Non-egc Superantigens from Staphylococcus aureus

Immune Cell Activation by Enterotoxin Gene Cluster (egc)-Encoded and Non-egc Superantigens from Staphylococcus aureus

Presymptomatic Prediction of Sepsis in Intensive Care Unit Patients

Transcriptome characterization of immune suppression from battlefield-like stress

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