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Logo of bmcmicrBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Microbiology
 
BMC Microbiol. 2012; 12: 79.
Published online May 20, 2012. doi:  10.1186/1471-2180-12-79
PMCID: PMC3430575
Cluster analysis of host cytokine responses to biodefense pathogens in a whole blood ex vivo exposure model (WEEM)
Brett A Chromy,corresponding author1,4 Imola K Fodor,2,5 Nancy K Montgomery,1 Paul A Luciw,3,4 and Sandra L McCutchen-Maloney1
1Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA, 94550, USA
2Computation Directorate, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA, 94550, USA
3Center for Comparative Medicine, University of California at Davis, Sacramento, CA, 95817, USA
4Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento, CA, 95817, USA
5Current address: Department of Biostatistics, Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA
corresponding authorCorresponding author.
Brett A Chromy: brett.chromy/at/ucdmc.ucdavis.edu; Imola K Fodor: fodor.imola/at/gene.com; Nancy K Montgomery: montgomery20/at/llnl.gov; Paul A Luciw: paluciw/at/ucdavis.edu; Sandra L McCutchen-Maloney: maloneyhome5/at/comcast.net
Received December 19, 2011; Accepted May 20, 2012.
Abstract
Background
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.
Results
Samples 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.
Conclusions
Cluster 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.
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