title: The involvement of IL-17A in the murine response to sub-lethal inhalational infection with Francisella tularensis.
abstract: BACKGROUND
  Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell-mediated immunity and IFNgamma in the host response to Francisella tularensis infection.
  
  
  RESULTS
  Here we provide evidence for the involvement of IL-17A in host defense to inhalational tularemia, using a mouse model of intranasal infection with the Live Vaccine Strain (LVS). We demonstrate the kinetics of IL-17A production in lavage fluids of infected lungs and identify the IL-17A-producing lymphocytes as pulmonary gammadelta and Th17 cells. The peak of IL-17A production appears early during sub-lethal infection, it precedes the peak of immune activation and the nadir of the disease, and then subsides subsequently. Exogenous airway administration of IL-17A or of IL-23 had a limited yet consistent effect of delaying the onset of death from a lethal dose of LVS, implying that IL-17A may be involved in restraining the infection. The protective role for IL-17A was directly demonstrated by in vivo neutralization of IL-17A. Administration of anti IL-17A antibodies concomitantly to a sub-lethal airway infection with 0.1xLD(50) resulted in a fatal disease.
  
  
  CONCLUSIONS
  In summary, these data characterize the involvement and underline the protective key role of the IL-17A axis in the lungs from inhalational tularemia.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Israel Institute of Biological Research, Ness Ziona, Israel.
authors.forename: Gal
authors.initials: G
authors.lastname: Markel
authors.forename: Erez
authors.initials: E
authors.lastname: Bar-Haim
authors.forename: Eran
authors.initials: E
authors.lastname: Zahavy
authors.forename: Hila
authors.initials: H
authors.lastname: Cohen
authors.forename: Ofer
authors.initials: O
authors.lastname: Cohen
authors.forename: Avigdor
authors.initials: A
authors.lastname: Shafferman
authors.forename: Baruch
authors.initials: B
authors.lastname: Velan
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000096:biosynthesis; D005604:Francisella tularensis / Q000276:immunology / Q000472:pathogenicity*; D019570:Inhalation Exposure; D020381:Interleukin-17 / Q000502:physiology*; D051379:Mice
chemical_list: D016207:Cytokines; D020381:Interleukin-17