title: 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.
authors.affiliation: Advanced Biomedical Computing Center, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: S
authors.initials: S
authors.lastname: Muhie
authors.affiliation: Integrative Systems Biology Program, US Army Center for Environmental Health Research, Frederick, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Hammamieh
authors.affiliation: College Park, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Cummings
authors.affiliation: Department of Chemistry, Georgetown University, Washington, DC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: Integrative Systems Biology Program, US Army Center for Environmental Health Research, Frederick, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Jett
mesh_terms: D000328:Adult; D017635:Clonal Anergy; D004768:Enterotoxins / Q000276:immunology*; D053263:Gene Regulatory Networks; D006801:Humans; D007962:Leukocytes / Q000276:immunology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D013315:Stress, Psychological / Q000235:genetics* / Q000276:immunology; D059467:Transcriptome
chemical_list: D004768:Enterotoxins; D035683:MicroRNAs; C031818:enterotoxin B, staphylococcal