title: Clearance of Aspergillus fumigatus is impaired in the airway in allergic inflammation.
abstract: BACKGROUND
  Aspergillus fumigatus (Af) sometimes colonizes and persists within the respiratory tree in some patients with asthma. To date, the precise reasons why the clearance of Af is impaired in patients with asthma remain unknown.
  
  
  OBJECTIVE
  To characterize the effects of allergic airway inflammation on clearance of Af.
  
  
  METHODS
  Control and Dermatophagoides farinae (Df) allergen-sensitized BALB/c mice were intranasally infected with Af. After 2 and 9 days of infection, the pathology, fungal burden, and cytokine profile in lung tissue were compared. In a different set of experiments, the phagocytotic activity of alveolar macrophages and the expression of their pathogen recognition receptors also were determined.
  
  
  RESULTS
  The Af conidia and neutrophilic airway inflammation disappeared by day 9 after infection in control mice. In Df-sensitized mice, Af conidia and neutrophilic and eosinophilic airway inflammation persisted at day 9 after infection. Compared with control mice, Df allergen-sensitized mice showed significant increases in interleukin (IL)-5 and decreases in IL-12 and interferon-γ in lung tissues at day 2 after infection. Most importantly, compared with Af-infected non-Df-sensitized mice, IL-17 in lung tissues was significantly decreased in Df allergen-sensitized Af-infected mice at day 2 after infection but was significantly increased at day 9. Alveolar macrophages isolated from Df allergen-sensitized mice exhibited significant decreases in phagocytotic activity and expression of Toll-like receptor-4 and dectin-1 compared with those from control mice.
  
  
  CONCLUSIONS
  In the airway of patients with allergy, T-helper cell type 2-dominant immunity potentially affects the expression of pathogen recognition receptors and attenuates cellular defense against Af. Prolonged IL-17 production also could play an important role.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Fukahori
authors.affiliation: Division of Respirology, Toho University Ohashi Medical Center, Tokyo, Japan. Electronic address: hiroto.matsuse@med.toho-u.ac.jp.
authors.forename: Hiroto
authors.initials: H
authors.lastname: Matsuse
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tsuchida
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawano
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Tomoya
authors.initials: T
authors.lastname: Nishino
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Chizu
authors.initials: C
authors.lastname: Fukushima
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D001228:Aspergillosis / Q000276:immunology* / Q000473:pathology; D001232:Aspergillus fumigatus / Q000276:immunology* / Q000472:pathogenicity; D001249:Asthma / Q000382:microbiology; D016535:Bronchial Hyperreactivity / Q000276:immunology* / Q000382:microbiology; D003550:Cystic Fibrosis / Q000382:microbiology; D040001:Dermatophagoides farinae / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D015848:Interleukin-5 / Q000276:immunology; D008168:Lung / Q000276:immunology; D016676:Macrophages, Alveolar / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018375:Neutrophil Activation / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000382:microbiology; D011657:Pulmonary Eosinophilia / Q000276:immunology; D012137:Respiratory System / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D039741:Antigens, Dermatophagoides; C508599:IL5 protein, human; D020381:Interleukin-17; D015848:Interleukin-5; D018664:Interleukin-12; D007371:Interferon-gamma