Transcriptome characterization of immune suppression from battlefield-like stress

Abstract

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.

Staphylococcal Enterotoxin B-Induced MicroRNA-155 Targets SOCS1 To Promote Acute Inflammatory Lung Injury

“…In humans, it has also been reported that soldiers undergoing a battlefield-like stress program demonstrated an increase in hsa-miR-155 levels in leukocytes exposed to SEB ex vivo (32), indicating that stress-related inflammation could also potentially lead to the increase in miR-155. The current study further suggests that the acute inflammatory response in the lungs to a bacterial superantigen is also regulated by miR-155, inasmuch as SEB-exposed miR-155 Ϫ/Ϫ mice having fewer infiltrating T cells than their WT counterparts and almost normal lung histopathology.…”

Stress-caused anergy of leukocytes towards Staphylococcal enterotoxin B and exposure transcriptome signatures

“…1 But complete and differential counts of post-RASP white blood cells (WBCs) are within normal ranges. 1 The compromised protective immunity and impaired response to the in vitro SEB challenge in spite of normal ranges of cell counts were considered to be indicators of the anergic state of post-RASP leukocytes to SEB. 1 The SEB toxin is a category B select agent 2 and a potent mitogen 3 with affinity to polymorphic major histocompatibility complex class II molecules with potential to stimulate different clones of T-cells.…”

“…1 Transcript mediators of compromised immunity remained suppressed in post-RASP leukocytes that are ex vivo exposed to Staphylococcal enterotoxin B (SEB). 1 But complete and differential counts of post-RASP white blood cells (WBCs) are within normal ranges.…”

“…1 Transcript mediators of compromised immunity remained suppressed in post-RASP leukocytes that are ex vivo exposed to Staphylococcal enterotoxin B (SEB). 1 But complete and differential counts of post-RASP white blood cells (WBCs) are within normal ranges. 1 The compromised protective immunity and impaired response to the in vitro SEB challenge in spite of normal ranges of cell counts were considered to be indicators of the anergic state of post-RASP leukocytes to SEB.…”

The expression of SLAMF7 levels in malignant B cells: a novel therapeutic pathway for patients with CLL

“…Protein kinase C (PKC) activators like phorbol esters and Bryostatins affect the signal transduction pathway, which has enormous effect on a variety of biological responses, which include proliferation and differentiation (Cambier and Ransom, 1987;King, 1988;Isakov et al, 1986;Muhie et al, 2013). Bryostatins are antipromoters of tumour cells (Hennings et al, 1990); hence they are more significant in clinical trials, than phorbol esters like phorbol myristate acetate (PMA), which are carcinogenic (Nishimoto et al, 2013;Hennings et al, 1987).…”