Transcriptional responses in spleens from mice exposed to Yersinia pestis CO92

Yersinia pestis is one of the most threatening biological agents due to the associated high mortality and history of plague pandemics. Identifying molecular players in the host response to infection may enable the development of medical countermeasures against Y. pestis. In this study, microarrays were used to identify the host splenic response mechanisms to Y. pestis infection. Groups of Balb/c mice were injected intraperitoneally with 2–257CFU of Y. pestis strain CO92 or vehicle. One group was assessed for mortality rates and another group for transcriptional analysis. The time to death at the 8 and 257CFU challenge doses were 5.0±2.3 and 3.8±0.4 days, respectively. Gene profiling using Affymetrix Mouse Genome 430 2.0 Arrays revealed no probe sets were significantly altered for all five mice in the low-dose group when compared to the vehicle controls. However, 534 probe sets were significantly altered in the high dose versus vehicle controls; 384 probe sets were down-regulated and 150 probe sets were up-regulated. The predominant biological processes identified were immune function, cytoskeletal, apoptosis, cell cycle, and protein degradation. This study provides new information on the underlying transcriptional mechanisms in mice to Y. pestis infection.