Transcriptional response signature of human lymphoid cells to staphylococcal enterotoxin B.
Two shock-inducing toxins that result in similar eventual outcome of disease were studied to determine host gene expression responses, for correlation of both similar and unique gene patterns. We initially used differential display (DD)-PCR and identified 859 cDNA fragments that were differentially expressed after 16 h of in vitro exposure of human peripheral blood mononuclear cells (PBMC) to staphylococcal enterotoxin B (SEB). Upon further examination using custom cDNA microarrays and RT-PCR analysis, we found unique set of genes to each toxin (SEB or lipopolysaccharide (LPS)), especially at early time periods. By 16 h, there was a convergence of some gene expression responses and many of those genes code for proteins such as proteinases, transcription factors, vascular tone regulators, and respiratory distress. In an attempt to replicate the findings in vivo, monkeys were challenged with SEB and the resultant gene expression responses indicated a pattern typical of SEB exposure when compared to LPS, with a similar outcome. We provide evidence that vastly diverse global gene analysis techniques used in unison can not only effectively identify pathogen-specific genomic markers and provide a solid foundation to mechanistic insights but also explain some of the toxin-related symptoms through gene functions.
Mendis
C
C
Division of Pathology, Walter Reed Army Institute of Research, Silver Spring, MD, USA. mendisc@uwplatt.edu
Das
R
R
Hammamieh
R
R
Royaee
A
A
Yang
D
D
Peel
S
S
Jett
M
M
D000818:Animals; D002478:Cells, Cultured; D004768:Enterotoxins / Q000633:toxicity*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D000882:Haplorhini; D006801:Humans; D007962:Leukocytes / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis
D004768:Enterotoxins; C031818:enterotoxin B, staphylococcal