title: Eosinophils are dispensable for allergic remodeling and immunity in a model of house dust mite-induced airway disease.
abstract: BACKGROUND
  Current thinking accredits eosinophils with preeminent contributions to allergic airway responses, including a major role in the development of airway remodeling, a process thought to significantly contribute to airway dysfunction. However, direct evidence in support of this notion is limited and often controversial.
  
  
  OBJECTIVE
  We elucidated the requirement for eosinophils in the generation of allergic sensitization, airway inflammation, and remodeling in a model involving chronic respiratory exposure to house dust mite (HDM).
  
  
  METHODS
  We used three methods to selectively eliminate eosinophils, a depleting antibody (anti-CCR3), and two strains of eosinophil-deficient mice (ΔdblGATA and the transgenic line PHIL).
  
  
  RESULTS
  Anti-CCR3 treatment markedly reduced pulmonary eosinophilia (> 80%) over the course of HDM exposure but had no effect on the remaining inflammatory response, the extent of lung Th2 cells, or the development of remodeling-associated changes, including subepithelial collagen deposition and smooth muscle thickening. In addition, we observed that, despite the absence of eosinophils, HDM-exposed GATA mice mounted robust airway and lung inflammation and hyperresponsiveness and showed a remodeling response equivalent to that observed in wild-type mice. Moreover, these mice had similar serum HDM-specific IgE levels and Th2-associated splenocyte cytokine production as HDM-exposed wild-type control mice. Similar observations were made in PHIL eosinophil-deficient mice subjected to chronic HDM exposure, although slight decreases in airway mononuclear cells, but not lung Th2 cells, and remodeling were noted.
  
  
  CONCLUSIONS
  Collectively, these data demonstrate that, at variance with the prevailing paradigm, eosinophils play negligible roles in the generation of HDM-induced allergic immunity and airway remodeling.
authors: Division of Respiratory Diseases and Allergy, Centre for Gene Therapeutics and Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.
authors: Ramzi
authors: R
authors: Fattouh
authors: Amal
authors: A
authors: Al-Garawi
authors: Marcia
authors: M
authors: Fattouh
authors: Katherine
authors: K
authors: Arias
authors: Tina D
authors: TD
authors: Walker
authors: Susanna
authors: S
authors: Goncharova
authors: Anthony J
authors: AJ
authors: Coyle
authors: Alison A
authors: AA
authors: Humbles
authors: Manel
authors: M
authors: Jordana
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D003094:Collagen / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000209:etiology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D039981:Pyroglyphidae / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism
chemical_list: D007073:Immunoglobulin E; D003094:Collagen