title: Eosinophil-derived IFN-gamma induces airway hyperresponsiveness and lung inflammation in the absence of lymphocytes.
abstract: BACKGROUND
  Eosinophils are key players in T(H)2-driven pathologies, such as allergic lung inflammation. After IL-5- and eotaxin-mediated tissue recruitment, they release several cytotoxic and inflammatory mediators. However, their exact contribution to asthma remains controversial. Indeed, in human subjects anti-IL-5 treatment inhibits eosinophilia but not antigen-induced airway hyperresponsiveness (AHR). Likewise, lung fibrosis is abrogated in 2 strains of eosinophil-deficient mice, whereas AHR is inhibited in only one of them. Finally, eosinophils have been shown to attract T(H)2 lymphocytes at the inflammatory site.
  
  
  OBJECTIVE
  The ability of eosinophils to promote AHR and lung inflammation independently of lymphocytes was investigated.
  
  
  METHODS
  Adoptive transfers of resting or activated eosinophils from IL-5 transgenic mice were performed into naive BALB/c mice, mice with severe combined immunodeficiency, and IFN-gamma-deficient BALB/c recipients.
  
  
  RESULTS
  Adoptively transferred eosinophils induced lung inflammation, fibrosis, collagen deposition, and AHR not only in BALB/c mice but also in recipient mice with severe combined immunodeficiency. Surprisingly, IFN-gamma expression was increased in lungs from eosinophil-transferred animals. Furthermore, IFN-gamma neutralization in recipients partially inhibited eosinophil-induced AHR. Moreover, IFN-gamma-deficient eosinophils or eosinophils treated with a blocking anti-IFN-gamma receptor antibody failed to induce AHR in IFN-gamma-deficient recipients. Finally, in vitro and at low concentrations, IFN-gamma increased eosinophil peroxidase release, potentiated chemotaxis, and prolonged survival, suggesting the existence of an autocrine mechanism.
  
  
  CONCLUSIONS
  These results support the important and previously unsuspected contribution of eosinophils to lung inflammation independently of lymphocytes through production of IFN-gamma, the prototypical T(H)1 cytokine.
authors.affiliation: Inserm U547, Lille, France; Institut Pasteur de Lille, Lille, France.
authors.forename: Akira
authors.initials: A
authors.lastname: Kanda
authors.forename: Virginie
authors.initials: V
authors.lastname: Driss
authors.forename: Nicolas
authors.initials: N
authors.lastname: Hornez
authors.forename: Marwan
authors.initials: M
authors.lastname: Abdallah
authors.forename: Thomas
authors.initials: T
authors.lastname: Roumier
authors.forename: Georges
authors.initials: G
authors.lastname: Abboud
authors.forename: Fanny
authors.initials: F
authors.lastname: Legrand
authors.forename: Delphine
authors.initials: D
authors.lastname: Staumont-Sallé
authors.forename: Severine
authors.initials: S
authors.lastname: Quéant
authors.forename: Julie
authors.initials: J
authors.lastname: Bertout
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fleury
authors.forename: Patrick
authors.initials: P
authors.lastname: Rémy
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Papin
authors.forename: Valérie
authors.initials: V
authors.lastname: Julia
authors.forename: Monique
authors.initials: M
authors.lastname: Capron
authors.forename: David
authors.initials: D
authors.lastname: Dombrowicz
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D002633:Chemotaxis / Q000276:immunology; D047209:Eosinophil Peroxidase / Q000032:analysis; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015848:Interleukin-5 / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D011014:Pneumonia / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D017471:Receptors, Interferon / Q000276:immunology / Q000378:metabolism
chemical_list: D015848:Interleukin-5; D017471:Receptors, Interferon; D007371:Interferon-gamma; D047209:Eosinophil Peroxidase