IFN-γ, but not IL-17A, is required for survival during secondary pulmonary Francisella tularensis Live Vaccine Stain infection.
IL-17 and IFN-γ 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-γ 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-γ and IL-17 during the secondary response to F. tularensis, we neutralized either IFN-γ or IL-17 in vivo using monoclonal antibody treatment. Vaccinated mice treated with anti-IFN-γ 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-γ 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.
Department of Immunobiology, University of Arizona, 1656 E. Mabel Street, MRB 218,Tucson, AZ 85718, United States.
Lydia M
LM
Roberts
Department of Immunobiology, University of Arizona, 1656 E. Mabel Street, MRB 218,Tucson, AZ 85718, United States.
John S
JS
Davies
Duke Human Vaccine Institute, 909 S. LaSalle Street, Durham, NC 27710, United States.
Gregory D
GD
Sempowski
Department of Immunobiology, University of Arizona, 1656 E. Mabel Street, MRB 218,Tucson, AZ 85718, United States. Electronic address: jfrelin@email.arizona.edu.
Jeffrey A
JA
Frelinger
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D058491:Bacterial Load; D001428:Bacterial Vaccines / Q000276:immunology*; D005260:Female; D005604:Francisella tularensis / Q000276:immunology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014406:Tularemia / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000276:immunology
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D020381:Interleukin-17; D014613:Vaccines, Attenuated; D007371:Interferon-gamma
Francisella tularensis; IL-17; Interferon-gamma; Intranasal; Secondary response; clpB