Transcriptional profiling of Francisella tularensis infected peripheral blood mononuclear cells: a predictive tool for tularemia.

In this study, we analyzed temporal gene expression patterns in human peripheral blood mononuclear cells (PBMCs) infected with the Francisella tularensis live vaccine strain from 1 to 24 h utilizing a whole human Affymetrix gene chip. We found that a considerable number of induced genes had similar expression patterns and functions as reported previously for gene expression profiling in patients with ulceroglandular tularemia. Among the six uniquely regulated genes reported for tularemia patients as being part of the alarm signal gene cluster, five, namely caspase 1, PSME2, TAP-1, GBP1, and GCH1, were induced in vitro. We also detected four out of the seven potential biomarkers reported in tularemia patients, namely TNFAIP6 at 4 h and STAT1, TNFSF10, and SECTM1 at 16 and 24 h. These observations underscore the value of using microarray expression profiling as an in vitro tool to identify potential biomarkers for human infection and disease. Our results indicate the potential involvement of several host pathways/processes in Francisella infection, notably those involved in calcium, zinc ion binding, PPAR signaling, and lipid metabolism, which further refines the current knowledge of F. tularensis infection and its effects on the human host. Ultimately, this study provides support for utilizing in vitro microarray gene expression profiling in human PBMCs to identify biomarkers of infection and predict in vivo immune responses to infectious agents.