Abstract
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.
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Acknowledgements
This work was supported by a Grant #DARPA-021-99, from Defense Advance Research Project Agency (DARPA). We like to extend our gratitude to Michael Hartl and Carla Sanchez (Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA) for their technical expertise and diligent work in carrying out the DD-PCR procedure.
Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, NRC Publication, 1996 edition.
Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the US Army.
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Mendis, C., Das, R., Hammamieh, R. et al. Transcriptional response signature of human lymphoid cells to staphylococcal enterotoxin B. Genes Immun 6, 84–94 (2005). https://doi.org/10.1038/sj.gene.6364160
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DOI: https://doi.org/10.1038/sj.gene.6364160
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