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Systemic Characterization of Immune Suppression from Battlefield‐like Stress

This study was designed to determine impact of battlefield‐like stress on the immune response using whole genome profiling and computational analyses. We collected whole blood samples from 15 US Army Ranger Training Battalion cadets before, and after 5 and 8 weeks training. Genome wide transcriptomes were analyzed using oligo‐nucleotide arrays representing ~24,700 human genes. More than 2300 differentially regulated genes were identified at both time points. Ontological enrichment showed suppression of transcripts important in microbial pattern recognition, inflammation, chemotaxis, and antigen preparation and presentations. Profiled genes and pathways were confirmed using both quantitative real time PCR arrays and high throughput ELISAs. Our computational analyses (for regulatory motifs and networks) identified the stress response site (STRE) as common regulatory motif of a number of profiled genes. Though, population of mono‐nuclear cells was not changed significantly, in vitro exposure of leucocytes to Staphylococcus enterotoxin B, a pyrogenic toxin, showed no response, and they seemed anergic. This may mean a highly compromised protective immune response. Suppression of most molecules involved in antigen presentation and lymphocytes' activation pathways may explain why individuals or animal models exposed to chronic stress show poor response towards proteineous antigen based vaccines.