title: Interleukin-17 protects against the Francisella tularensis live vaccine strain but not against a virulent F. tularensis type A strain.
abstract: Francisella tularensis is a highly infectious intracellular bacterium that causes the zoonotic infection tularemia. While much literature exists on the host response to F. tularensis infection, the vast majority of work has been conducted using attenuated strains of Francisella that do not cause disease in humans. However, emerging data indicate that the protective immune response against attenuated F. tularensis versus F. tularensis type A differs. Several groups have recently reported that interleukin-17 (IL-17) confers protection against the live vaccine strain (LVS) of Francisella. While we too have found that IL-17Rα(-/-) mice are more susceptible to F. tularensis LVS infection, our studies, using a virulent type A strain of F. 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 than F. tularensis type 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 A F. tularensis infection, and that induced and protective immunity differs between attenuated and virulent strains of F. tularensis.
authors.affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, USA. skybergj@missouri.edu
authors.forename: Jerod A
authors.initials: JA
authors.lastname: Skyberg
authors.forename: Maryclare F
authors.initials: MF
authors.lastname: Rollins
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Samuel
authors.forename: Marjorie D
authors.initials: MD
authors.lastname: Sutherland
authors.forename: John T
authors.initials: JT
authors.lastname: Belisle
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology* / Q000494:pharmacology*; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology; D005260:Female; D005604:Francisella tularensis / Q000276:immunology* / Q000472:pathogenicity; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D020381:Interleukin-17 / Q000235:genetics* / Q000276:immunology*; D053760:Interleukin-23 Subunit p19 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D053722:Receptors, Interleukin-17 / Q000276:immunology; D014406:Tularemia / Q000235:genetics* / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000276:immunology / Q000494:pharmacology
chemical_list: D001428:Bacterial Vaccines; C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19; D053722:Receptors, Interleukin-17; D014613:Vaccines, Attenuated; D007371:Interferon-gamma; D020170:Caspase 1