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Indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

ABSTRACT: gene expression host responses to biological threat agents in human PBMC Keywords: pathogen response

ORGANISM(S): Homo sapiens

PROVIDER: GSE4478 | GEO | 2006/05/19

SECONDARY ACCESSION(S): PRJNA94349

REPOSITORIES: GEO

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Indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells

Project description:gene expression host responses to biological threat agents in human PBMC PBMC were exposed to various pathgens at different time points

2010-07-01 | E-GEOD-4478 | biostudies-arrayexpress

Early indicators of exposure to biological threat agents using host gene profiles in peripheral blood mononuclear cells.

Project description:BACKGROUND: Effective prophylaxis and treatment for infections caused by biological threat agents (BTA) rely upon early diagnosis and rapid initiation of therapy. Most methods for identifying pathogens in body fluids and tissues require that the pathogen proliferate to detectable and dangerous levels, thereby delaying diagnosis and treatment, especially during the prelatent stages when symptoms for most BTA are indistinguishable flu-like signs. METHODS: To detect exposures to the various pathogens more rapidly, especially during these early stages, we evaluated a suite of host responses to biological threat agents using global gene expression profiling on complementary DNA arrays. RESULTS: We found that certain gene expression patterns were unique to each pathogen and that other gene changes occurred in response to multiple agents, perhaps relating to the eventual course of illness. Nonhuman primates were exposed to some pathogens and the in vitro and in vivo findings were compared. We found major gene expression changes at the earliest times tested post exposure to aerosolized B. anthracis spores and 30 min post exposure to a bacterial toxin. CONCLUSION: Host gene expression patterns have the potential to serve as diagnostic markers or predict the course of impending illness and may lead to new stage-appropriate therapeutic strategies to ameliorate the devastating effects of exposure to biothreat agents.

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The Impact of Blood-Processing Time on the Proteome of Human Peripheral Blood Mononuclear Cells

Project description:Human peripheral blood mononuclear cells (PBMC) are key to several diagnostics assays and basic science research. Blood pre-analytical variations that occur before obtaining the PBMC fraction can have a significant impact on the results of the assays, including viability, composition, integrity, and gene expression changes of immune cells. With this as motivation, we performed a quantitative shotgun proteomics analysis using Isobaric Tag for Relative and Absolute Quantitation (iTRAQ 8plex) labeling to compare PBMC obtained from fresh versus 24h-stored blood at room temperature. We identified 3,195 proteins, of which 245 were differentially abundant. Our results revealed enriched pathways in the fresh-PBMC samples related to exocytosis, localization, vesicle-mediated transport, cell activation, and secretion. In contrast, pathways related to exocytosis, neutrophil degranulation and activation, granulocyte activation, leukocyte degranulation, and myeloid leukocyte activation involved in immune response were enriched in the 24h-PBMC samples, which may indicate probable granulocyte contamination and activation due to blood storage time and temperature. Examples of upregulated proteins in the 24h-PBMC sample are: CAMP, S100A8, LTA4H, RASAL3, and S100A6, which are involved in an adaptive immune system and antimicrobial activity, proinflammatory mediation, aminopeptidase activities, and naïve T cells survival. Moreover, examples of downregulated proteins are: NDUFA5, TAGLN2, H3C1, TUBA8, and CCT2 that are related to the cytoskeleton, cell junction, mitochondrial respiratory chain. In conclusion, blood-processing time directly impacts the proteomic profile of human PBMC.

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