Identification of Early Interactions between Francisella and the Host

The adaptive immune response toFrancisella tularensis is dependent on the route of inoculation. Intradermal inoculation with theF. tularensis live vaccine strain (LVS) results in a robust Th1 response in the lungs, whereas intranasal inoculation produces fewer Th1 cells and instead many Th17 cells. Interestingly, bacterial loads in the lungs are similar early after inoculation by these two routes. We hypothesize that the adaptive immune response is influenced by local events in the lungs, such as the type of cells that are first infected withFrancisella . Using fluorescence-activated cell sorting, we identified alveolar macrophages as the first cell type infected in the lungs of mice intranasally inoculated withF. novicida U112, LVS, orF. tularensis Schu S4. Following bacterial dissemination from the skin to the lung, interstitial macrophages or neutrophils are infected. Overall, we identified the early interactions betweenFrancisella and the host following two different routes of inoculation.