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

被引:6
作者
Chromy, Brett A. [1 ,2 ]
Fodor, Imola K. [3 ]
Montgomery, Nancy K. [1 ]
Luciw, Paul A. [2 ,4 ]
McCutchen-Maloney, Sandra L. [1 ]
机构
[1] Lawrence Livermore Natl Lab, Phys & Life Sci Directorate, Livermore, CA 94550 USA
[2] Univ Calif Davis, Sch Med, Dept Pathol & Lab Med, Sacramento, CA 95817 USA
[3] Lawrence Livermore Natl Lab, Computat Directorate, Livermore, CA 94550 USA
[4] Univ Calif Davis, Ctr Comparat Med, Sacramento, CA 95817 USA
关键词
ENTEROCOLITICA INVASIN PROTEIN; NECROSIS-FACTOR-ALPHA; ANTHRACIS LETHAL TOXIN; YERSINIA-PESTIS; EPITHELIAL-CELLS; PROINFLAMMATORY CYTOKINES; EVOLUTIONARY GENOMICS; DENDRITIC CELLS; III SECRETION; MOUSE MODEL;
D O I
10.1186/1471-2180-12-79
中图分类号
Q93 [微生物学];
学科分类号
071005 [微生物学];
摘要
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-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IP-10, MCP-1 and TNF alpha, 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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页数:9
相关论文
共 60 条
[1]
Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis [J].
Achtman, M ;
Zurth, K ;
Morelli, C ;
Torrea, G ;
Guiyoule, A ;
Carniel, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (24) :14043-14048
[2]
Microevolution and history of the plague bacillus, Yersinia pestis [J].
Achtman, M ;
Morelli, G ;
Zhu, PX ;
Wirth, T ;
Diehl, I ;
Kusecek, B ;
Vogler, AJ ;
Wagner, DM ;
Allender, CJ ;
Easterday, WR ;
Chenal-Francisque, V ;
Worsham, P ;
Thomson, NR ;
Parkhill, J ;
Lindler, LE ;
Carniel, E ;
Keim, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (51) :17837-17842
[3]
Anisimov AP, 2007, ADV EXP MED BIOL, V603, P23
[4]
EFFECTS OF LISTERIA-MONOCYTOGENES AND YERSINIA-ENTEROCOLITICA ON CYTOKINE GENE-EXPRESSION AND RELEASE FROM HUMAN POLYMORPHONUCLEAR GRANULOCYTES AND EPITHELIAL (HEP-2) CELLS [J].
ARNOLD, R ;
SCHEFFER, J ;
KONIG, B ;
KONIG, W .
INFECTION AND IMMUNITY, 1993, 61 (06) :2545-2552
[5]
Innate Immune Recognition of Yersinia pseudotuberculosis Type III Secretion [J].
Auerbuch, Victoria ;
Golenbock, Douglas T. ;
Isberg, Ralph R. .
PLOS PATHOGENS, 2009, 5 (12)
[6]
Human chemokines: An update [J].
Baggiolini, M ;
Dewald, B ;
Moser, B .
ANNUAL REVIEW OF IMMUNOLOGY, 1997, 15 :675-705
[7]
Macrophage activation redirects Yersinia-infected host cell death from apoptosis to caspase-1-dependent pyroptosis [J].
Bergsbaken, Tessa ;
Cookson, Brad T. .
PLOS PATHOGENS, 2007, 3 (11) :1570-1582
[8]
Innate immune response during Yersinia infection: critical modulation of cell death mechanisms through phagocyte activation [J].
Bergsbaken, Tessa ;
Cookson, Brad T. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2009, 86 (05) :1153-1158
[9]
Bioterrorism: management of major biological agents [J].
Bossi, P. ;
Garin, D. ;
Guihot, A. ;
Gay, F. ;
Crance, J. -M. ;
Debord, T. ;
Autran, B. ;
Bricaire, F. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2006, 63 (19-20) :2196-2212
[10]
Interleukin-10 and inhibition of innate immunity to yersiniae: Roles of Yops and LcrV (V antigen) [J].
Brubaker, RR .
INFECTION AND IMMUNITY, 2003, 71 (07) :3673-3681