Route of Francisella tularensis infection shapes the subsequent immune response (99.2)

Abstract

Abstract The bacterium Francisella tularensis is the causative agent of tularemia. F. tularensis induces a host response that is dependent on the route of infection. Intranasal (i.n.) inoculations are more virulent and require fewer bacteria to produce a lethal infection than intradermal (i.d.) inoculations (10^3 organisms i.n. versus 10^6 i.d.). Interestingly, one day post infection, the bacterial loads are similar in the spleen and lung regardless of the route of infection. We also found that i.d. inoculation resulted in IFN-γ+ T cells in the lung whereas i.n. inoculation produced very few IFN-γ+ T cells and instead many IL-17+ T cells in the lung. Due to the similar bacterial loads systemically after 1 day, but very different host responses, we hypothesize that the adaptive immune response is influenced by local events at the site of infection immediately following inoculation. To test this hypothesis, we infected C57Bl/6 mice i.n. or i.d. and identified cytokine production in the lung and tail at four hours post-infection. Additionally, we have identified alveolar macrophages as the primary cell type infected four hours post-infection, to the exclusion of other myeloid cells and lung parenchyma. Furthermore, we have identified cytokines produced by alveolar macrophages when cultured ex vivo and infected with F. tularensis. These data will help us further understand how the adaptive immune response to F. tularensis is shaped early after infection.