Characterization of Neuroinflammatory Response in BALB/c Mice After Exposure to Aerosolized Yersinia pestis 2253118

Abstract Introduction Plague, caused by the bacterium Yersinia pestis, can present as several forms including bubonic, septicemic, pneumonic, and meningitis. Plague meningitis is considered rare and has been estimated to occur in 6-11% of documented cases, mostly observed in pediatric patients 15 years old or younger. Furthermore, most cases are tied to inadequate or no antibiotic treatment of bubonic cases. To date, there have been few reports describing neurologic plague in the mouse model of pneumonic plague. Methods We used the BALB/c mouse model of exposure to aerosolized Y. pestis to characterize the pathogenic effects in the CNS resulting from pneumonic plague. Here we use a multifaceted approach analyzing tissue homogenates, tissue slides, transcriptomic, and cytokine data of mice exposed to aerosolized Y. pestis CO92, collected at 24-hour intervals for three days. Results We find that Y. pestis is present in brain homogenates, but histology indicates that it is bound to the capillaries inside the cerebellum, cerebrum, and nasal turbinates. However, transcriptomic data targeting mouse neuroinflammatory responses indicates dysregulation of several gene pathways including those associated with CNS cells such as astrocytes, oligodendrocytes, and microglia. Furthermore, there is a cytokine response to pneumonic plague in brain tissues. Conclusion Although Y. pestis does not breach the capillaries resulting in meningitis in our model, we find evidence of a neuroinflammatory response within the CNS of mice. Funding Source DTRA-JSTO Topic Categories Neuroimmunology (NEUR)