Stress-caused anergy of leukocytes towards staphylococcal enterotoxin b and exposure transcriptome signatures

ABSTRACT Leucocytes from soldiers exposed to battlefield-like stress (RASP: Rangers Assessment and Selection Program) were exposed _in vitro_ to _Staphylococcal enterotoxin_ B (SEB). We

assayed SEB-induced regulation of gene expression, both in the presence and absence of severe stress, to generate two sets of gene profiles. One set of transcripts and microRNAs were

specific to post-RASP SEB exposure, and another set were signatures of SEB exposure common to both the pre- and post-RASP leucocytes. Pathways and upstream regulatory analyses indicated that

the post-RASP SEB-signature transcripts were manifestation of the anergic state of post-RASP leucocytes. These were further verified using expression-based predictions of cellular processes

and literature searches. Specificity of the second set of transcripts to SEB exposure was verified using machine-learning algorithms on our and four other (Gene Expression Omnibus) data

sets. Cell adhesion, coagulation, hypoxia and vascular endothelial growth factor-mediated vascular leakage were SEB-specific pathways even under the background of severe stress.

Hsa-miR-155-3p was the top SEB exposure predictor in our data set, and C-X-C motif chemokine ligand 9 was SEB specific in all the analyzed data sets. The SEB-signature transcripts (which

also showed distinct expression signatures from _Yersinia pestis_ and dengue virus) may serve as potential biomarkers of SEB exposure even under the background of stress. Access through your

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SIMILAR CONTENT BEING VIEWED BY OTHERS ALTERED GENE EXPRESSION AND PTSD SYMPTOM DIMENSIONS IN WORLD TRADE CENTER RESPONDERS Article 17 February 2022 INTEGRATION OF PERIPHERAL

TRANSCRIPTOMICS, GENOMICS, AND INTERACTOMICS FOLLOWING TRAUMA IDENTIFIES CAUSAL GENES FOR SYMPTOMS OF POST-TRAUMATIC STRESS AND MAJOR DEPRESSION Article 07 May 2021 SINGLE-CELL ANALYSIS

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2005; 21: 3448–3449. Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank Julia Scheerer and Allison Hoke for editing the manuscript and for their invaluable comments.

We are grateful to The Defense Threat Reduction Agency for funding. HUMAN SUBJECTS PROTECTION Research was conducted in compliance with IRB-approved human subjects protocol—no.1014 for

initial collection of samples and A-16815 for continuation of data evaluation. The human use approval was obtained from the local Protection of Human subjects Office and further approved by

the Human Research Protection Office, Office of Research Protections, US Army Medical Research and Materiel Command, Fort Detrick, MD, USA. DISCLAIMER The views, opinions, and/or findings

contained in this report are those of the authors and should not be construed as official Department of the Army position, policy or decision, unless so designated by other official

documentation. Citations of commercial organizations or trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of

these organizations. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Frederick, MD, USA S Muhie *

Integrative Systems Biology Program, US Army Center for Environmental Health Research, Frederick, MD, USA R Hammamieh & M Jett * College Park, MD, USA C Cummings * Department of

Chemistry, Georgetown University, Washington, DC, USA D Yang Authors * S Muhie View author publications You can also search for this author inPubMed Google Scholar * R Hammamieh View author

publications You can also search for this author inPubMed Google Scholar * C Cummings View author publications You can also search for this author inPubMed Google Scholar * D Yang View

author publications You can also search for this author inPubMed Google Scholar * M Jett View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING

AUTHOR Correspondence to M Jett. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies this paper

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Muhie, S., Hammamieh, R., Cummings, C. _et al._ Stress-caused anergy of leukocytes towards _Staphylococcal enterotoxin_ B and exposure transcriptome signatures. _Genes Immun_ 16, 330–346

(2015). https://doi.org/10.1038/gene.2015.16 Download citation * Received: 05 December 2014 * Revised: 27 March 2015 * Accepted: 31 March 2015 * Published: 28 May 2015 * Issue Date: July

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