IFN-γ, but not IL-17A, is required for survival during secondary pulmonary Francisella tularensis Live Vaccine Stain infection

IL-17 and IFN-gamma production by Th17 and Th1 cells, respectively, is critical for survival during primary respiratory infection with the pathogenic bacterium, Francisella tularensis Live Vaccine Strain (LVS). The importance, however, of these T cell subsets and their soluble mediators is not well understood during a secondary or memory response. We measured the number of CD4(+) T cells producing IFN-gamma or IL-17 in the spleen and lungs of vaccinated mice on day four of the secondary response using intracellular cytokine staining in order to identify protective T cell subsets participating in the memory response. Few bacteria were present in spleens of vaccinated mice on day four and a T cell response was not observed. In the lung, where more bacteria were present, there was a robust Th1 response in vaccinated mice but Th17 cells were not present at higher numbers in vaccinated mice compared to unvaccinated mice. These data show that the lung is the dominant site of the secondary immune response and suggest that Th17 cells are not required for survival during secondary challenge. To further investigate the importance of IFN-gamma and IL-17 during the secondary response to F. tularensis, we neutralized either IFN-gamma or IL-17 in vivo using monoclonal antibody treatment. Vaccinated mice treated with anti-IFN-gamma lost more weight and had higher bacterial burdens compared to vaccinated mice treated with isotype control antibody. In contrast, treatment with anti-IL-17A antibody did not alter weight loss profiles or bacterial burdens compared to mice treated with isotype control antibody. Together, these results suggested that IFN-gamma is required during both primary and secondary respiratory F. tularensis infection. IL-17, on the other hand, is only critical during the primary response to respiratory F. tularensis but dispensable during the secondary response. (C) 2014 Elsevier Ltd. All rights reserved.