Using Tissue Culture to Model Early Events in Francisella tularensis Pathogenesis

Abstract: Francisella tularensis is a highly infectious bacterium that causes tularemia or rabbit fever. The infectious dose is as low as 10 CFU. While a lot of F. tularensis research focuses on macrophages, lung epithelium cells may be important too. There are far more epithelial cells on the surface of the lungs than macrophages. With such a low infectious dose, it is more likely for F. tularensis to infect an epithelial cell than macrophage. I found that F. tularensis has similar growth rates in human alveolar epithelial cells (A549) as murine macrophages (J774) after initial infection. Also, I have demonstrated that F. tularensis can infect human primary bronchial epithelium (HBE) in a 3D culture system that mimics airway architecture in the lung. The data suggests that it takes F. tularensis longer to infect the HBE cells than the A549 or J774 cells. I have worked to develop a protocol for infecting HBE cells with F. tularensis. The pathogenesis in rabbit lung tissue was assessed too. Over the course of the first three days post-exposure there is an increasing amount of inflammation, hemorrhaging and apoptosis in the lower left lung of rabbits. When taken all together, this data suggests lung epithelial cells could have a role in F. tularensis early pathogenesis and dissemination. 

Advisor: Douglas Reed