Abstract
BackgroundRapid detection and therapeutic intervention for infectious and emerging diseases is a major scientific goal in biodefense and public health. Toward this end, cytokine profiles in human blood were investigated using a human whole blood ex vivo exposure model, called WEEM.ResultsSamples of whole blood from healthy volunteers were incubated with seven pathogens including Yersinia pseudotuberculosis, Yersinia enterocolitica, Bacillus anthracis, and multiple strains of Yersinia pestis, and multiplexed protein expression profiling was conducted on supernatants of these cultures with an antibody array to detect 30 cytokines simultaneously. Levels of 8 cytokines, IL-1α, IL-1β, IL-6, IL-8, IL-10, IP-10, MCP-1 and TNFα, were significantly up-regulated in plasma after bacterial exposures of 4 hours. Statistical clustering was applied to group the pathogens based on the host response protein expression profiles. The nearest phylogenetic neighbors clustered more closely than the more distant pathogens, and all seven pathogens were clearly differentiated from the unexposed control. In addition, the Y. pestis and Yersinia near neighbors were differentiated from the B. anthracis strains.ConclusionsCluster analysis, based on host response cytokine profiles, indicates that distinct patterns of immunomodulatory proteins are induced by the different pathogen exposures and these patterns may enable further development into biomarkers for diagnosing pathogen exposure.
Highlights
Rapid detection and therapeutic intervention for infectious and emerging diseases is a major scientific goal in biodefense and public health
Infections caused by Y. pseudotuberculosis or Y. enterocolitica can be effectively treated with antibiotics and in most cases are self-limiting
Bacterial strains and culture conditions The bacterial strains used in this study include: B. anthracis Ames, B. anthracis Sterne, Y. pestis KIM5 D27
Summary
Rapid detection and therapeutic intervention for infectious and emerging diseases is a major scientific goal in biodefense and public health Toward this end, cytokine profiles in human blood were investigated using a human whole blood ex vivo exposure model, called WEEM. The microorganism possesses a Type III secretion mechanism common to several human, animal and plant pathogens, whereby a series of pathogenspecific structural proteins form a syringe-like structure capable of injecting virulence factors into the mammalian host cell. These virulence factors facilitate pathogen use of host nutrients and thwart the host immune response, Two other species from the genus Yersinia are human pathogens: Y. pseudotuberculosis and Y. enterocolitica [9,10]. Y. pestis is reported to have evolved from Y. pseudotuberculosis within the past 10,000 years [11]
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