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Francisella tularensis is a zoonotic, facultative intracellular bacterial pathogen capable of initiating infection, tularemia, via multiple routes including dermal micro-abrasions and inhalation. Mouse models of systemically-initiated infection with F. tularensis LVS have been used extensively to reveal potential host defence mechanisms against the pathogen. Such studies have demonstrated the critical need for neutrophils and interferon-gamma (IFN-γ) to combat the early stages of primary experimental tularaemia initiated by systemic routes. Surprisingly, however, the present study shows that these defences appear not to combat early pulmonary tularaemia initiated by inhalation of the pathogen into the lower airways. The results imply that the effectiveness of particular anti-bacterial host defences vary with invasion site. Thus, it is impossible to predict effective host defence mechanisms against inhalation-initiated …