Macrophage subsets determine sex differences between male and female immune responses to Francisella tularensis

Abstract

Francisella tularensisis the causative agent of the human disease tularemia. F. tularensisinfects a variety of cells, including macrophages, in order to cause pathogenicity. As few as 10 inhaled microorganisms cause a lethal infection by over-activating the host’s own inflammatory response. Differences in the intensity of the inflammatory response exist between the sexes which leads to differences in sensitivity to autoimmune and infectious disease. Males tend to be more susceptible to infectious diseases whereas females tend to be more susceptible to autoimmune diseases. However, our preliminary data unexpectedly demonstrated that female mice were more susceptible to F. tularensis-mediated disease than male mice. We hypothesize that the elevated inflammatory state of females may make them more susceptible to F. tularensis disease and that the M1 and M2 macrophage subsets may determine this differential inflammatory response. Naïve M1 and M2 macrophages will be purified from male and female mice and infected in vitro to directly compare cellular responses between male and female mice. In parallel, M0 macrophages will be differentiated in vitro prior to infection for similar comparison.