Persistence of Host Response Signatures of Pathogens Despite Evidence of Stress‐Induced Immune Suppression

Abstract

The aim of this study was to determine the impact of battlefield-like stress on immune function and to determine if host genomic responses to dengue, plague and staphylococcal enterotoxin B (SEB) can still predict such exposures despite the “background” effects of immune suppression due to stress. Leucocytes isolated from blood samples of 15 US Army Ranger Training Battalion (RTB) Cadets (collected before and after 8 weeks training) were exposed in vitro to the three pathogens to analyze pathogen- and/or stress-induced regulation of gene expression profiles using cDNA arrays of ~9,000 human gene probes. After the RTB course, trainees had lost weight and showed metabolite patterns of severe stress. Statistically significant host response genes both in the presence and absence of the RTB stressors were determined. In each case of the matched pairs of before/after training, the gene profiles showed consistent suppression of immune related genes. Though a number of genes showed regulation when RTB stressors acted alone or in concert with pathogenesis, yet we were able to identify other genes that showed consistent differential expression specific to dengue, plague and SEB both before and after RTB stressors. Some of the significantly regulated genes are involved in defense, stress response, signal transduction, transcriptional and growth regulations. We are grateful to the Defense Threat Reduction Agency for funding.