SEB‐induced host gene expression in peripheral blood mononuclear cells in vitro and in vivo in piglets

Staphylococcal enterotoxins (SEs) constitute a family of proteins that bind to T‐cell receptors and major histocompatibility antigen complexes and induce massive activation of T cells in the host. Since human clinical cases of illness induced by some pathogens are, fortunately, rare, use of animal models that closely mimic the human illness is the only in vivo option. Such studies can be very difficult and expensive, therefore, maximizing the information obtained from in vitro exposures to peripheral blood mononuclear cells (PBMCs) provide an opportunity to investigate dose/time variability in host responses. We studied gene expression patterns in human PBMCs exposed to staphylococcal enterotoxin B (SEB) in vitro and compared the in vitro data with data obtained in vivo using PBMCs from a piglet model of SEB intoxication that closely replicates the progression of illness in humans. We applied a supervised learning method for class prediction based on the k‐nearest neighbor algorithm for the data obtained in piglets exposed to SEB in vivo against a training data set. This data set included gene expression profiles derived from in vitro exposures to eight different pathogens (Bacillus anthracis, Yersinia pestis, Brucella melitensis, SEB, Cholera toxin, Clostridium botulinum toxin A, Venezuelan equine encephalitis, and Dengue‐2) in PBMCs. We found that despite differences in gene expression profiles between in vitro and in vivo systems, there exists a subset of genes that show correlations between in vitro and in vivo exposures which can be used as a predictor of exposure to SEB in vivo.