Cluster analysis of host cytokine responses to biodefense pathogens in a whole blood ex vivo exposure model (WEEM)

Chromy, Brett A.; Fodor, Imola K.; Montgomery, Nancy K.; Luciw, Paul A.; McCutchen-Maloney, Sandra L.

doi:10.1186/1471-2180-12-79

Cluster analysis of host cytokine responses to biodefense pathogens in a whole blood ex vivo exposure model (WEEM)

Journal Article · Sun May 20 00:00:00 EDT 2012 · BMC Microbiology

DOI:https://doi.org/10.1186/1471-2180-12-79· OSTI ID:1626479

Chromy, Brett A. ^[1]; Fodor, Imola K. ^[2]; Montgomery, Nancy K. ^[3]; Luciw, Paul A. ^[4]; McCutchen-Maloney, Sandra L. ^[3]

Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical and Life Sciences Directorate; Univ. of California, Davis, Sacramento, CA (United States). School of Medicine. Dept. of Pathology and Lab. Medicine; DOE/OSTI
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Computation Directorate
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Physical and Life Sciences Directorate
Univ. of California, Davis, Sacramento, CA (United States). Center for Comparative Medicine; Univ. of California, Davis, Sacramento, CA (United States). School of Medicine. Dept. of Pathology and Lab. Medicine

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1626479

Journal Information:: BMC Microbiology, Journal Name: BMC Microbiology Journal Issue: 1 Vol. 12; ISSN 1471-2180

Publisher:: BioMed CentralCopyright Statement

Country of Publication:: United States

Language:: English

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