The heightened inflammatory response makes females are more susceptible to F. tularensis-mediated death (INM1P.444)

The zoonotic infectious disease, Francisella tularensis , the causative agent for human tularemia, elicits high cytokine levels as a result of rampant inflammation, a condition referred to as “cytokine storm.” This cytokine storm is responsible for the severity of symptoms and ultimately for the death of the host. Though men have a tendency to be exposed to the pathogen more frequently than women, do to its presence in wild animals, women have a significantly greater inflammatory response than do men. Therefore, we asked whether their enhanced inflammatory response might make women more susceptible to tularemia-mediated death. Male and female mice were infected with F. tularensis and their survival and inflammatory response monitored. Subsequently, the role of sex hormones was considered by infecting gonadectomized mice. On average, 15% female mice survived infection compared with 90% of male mice. In addition, the female mice displayed an increased serum cytokine storm compared with male mice despite similar levels of bacterial growth. We seek to identify the factors controlling this increased susceptibility of female mice. This line of investigation may lead to the development of novel therapeutics and/or treatment strategies specific to women exposed to F. tularensis .