1. ¹Department of Molecular Pathology, Walter Reed Army Institute of Research, Silver Spring, MD, USA
2. ²Department of Bacterial Diseases, Walter Reed Army Institute of Research, Silver Spring, MD, USA

Correspondence: Dr M Jett, Division of Pathology, Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. E-mail: marti.jett@us.army.mil

Received 11 September 2006; Revised 12 February 2007; Accepted 14 February 2007; Published online 12 April 2007.

Abstract

Yersinia pestis, the causative agent of plague, is known to develop strategies to overcome the host immune mechanisms and survive in the host. The molecular changes induced by Y. pestis in the host are not well delineated. Here, we examined the early events triggered after the intracellular infection of Y. pestis in human monocytes and lymphocytes by analyzing the host transcriptional profiles using cDNA arrays. We found that sets of genes that, especially at early time periods, were highly upregulated in monocytes alone when compared with a mixed culture of lymphocytes and monocytes. Gene expression responses revealed genes coding for cytokines, chemokines, transcription factors, inflammatory and apoptosis-related genes. Protein levels were measured, and real-time polymerase chain reaction was used to validate the microarray results. Our data suggest that intracellular infection of human monocytes with Y. pestis results in a strong inflammatory response at early time periods and a downregulation of genes such as thromobomodulin, which may play a role in coagulation, resulting in disseminated intravascular coagulation, a primary cause of death in plague infected hosts. We provide evidence that genomic analysis can provide a solid foundation to mechanistic insights to explain some of the symptoms induced by Y. pestis.