Differential susceptibility of Sprague-Dawley and Fischer 344 rats to infection by Francisella tularensis

The type A and B subspecies of Francisella tularensis cause severe disease, tularemia, in humans. However, only the former can be lethal especially if inhaled. It is likely that non-lethal infection is due at least in part to the ability of innate host defenses to control pathogen growth whilst acquired immunity develops. Most common small laboratory animals rapidly succumb to clinical strains of E tularensis and are, therefore, poor models with which to study innate immunity. In an attempt to improve upon this situation in the present study, Sprague-Dawley and Fischer 344 rats were examined for their ability to combat challenge with type A and B strains of the pathogen. Sprague-Dawley rats were significantly more resistant than Fischer rats to infection with either subspecies. This correlated with the ability of Sprague-Dawley rats to arrest the growth of the pathogen at both the site of challenge and at sites of disseminated infection. The rapidity with which E tularensis kills susceptible rats and the early onset of control of infection in resistant rats suggests that differences in innate immunity account for these disparate outcomes. Thus, the rat might be a more useful model for studying innate immunity to virulent E tularensis than other small mammals. Crown Copyright (C) 2009 Published by Elsevier Ltd. All rights reserved.