Interleukin-17 Protects against the Francisella tularensis Live Vaccine Strain but Not against a Virulent F. tularensis Type A Strain
ABSTRACTFrancisella tularensisis a highly infectious intracellular bacterium that causes the zoonotic infection tularemia. While much literature exists on the host response toF. tularensisinfection, the vast majority of work has been conducted using attenuated strains ofFrancisellathat do not cause disease in humans. However, emerging data indicate that the protective immune response against attenuatedF. tularensisversusF. tularensistype A differs. Several groups have recently reported that interleukin-17 (IL-17) confers protection against the live vaccine strain (LVS) ofFrancisella. While we too have found that IL-17Rα−/−mice are more susceptible toF. tularensisLVS infection, our studies, using a virulent type A strain ofF. tularensis(SchuS4), indicate that IL-17Rα−/−mice display organ burdens and pulmonary gamma interferon (IFN-γ) responses similar to those of wild-type mice following infection. In addition, oral LVS vaccination conferred equivalent protection against pulmonary challenge with SchuS4 in both IL-17Rα−/−and wild-type mice. While IFN-γ was found to be critically important for survival in a convalescent model of SchuS4 infection, IL-17 neutralization from either wild-type or IFN-γ−/−mice had no effect on morbidity or mortality in this model. IL-17 protein levels were also higher in the lungs of mice infected with the LVS rather thanF. tularensistype A, while IL-23p19 mRNA expression was found to be caspase-1 dependent in macrophages infected with LVS but not SchuS4. Collectively, these results demonstrate that IL-17 is dispensable for host immunity to type AF. tularensisinfection, and that induced and protective immunity differs between attenuated and virulent strains ofF. tularensis.