title: Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways.
abstract: BACKGROUND
  Allergic rhinitis (AR) and asthma are 2 entities of allergic airway diseases that frequently occur together, which is referred to as united airways. In contrast to this general concept, we hypothesized that innate immunity of the upper and lower airways is respectively distinctive, because the immunologic conditions of the nasal and lung mucosa as well as the functions of the immune cells within their epithelia are different.
  
  
  OBJECTIVE
  We wanted to identify distinctive mechanisms of innate immunity in the nose and lung mucosa, which are responsible for house dust mite (HDM)-induced AR and allergic asthma (AA), respectively.
  
  
  METHODS
  We constructed a mouse model of AR or AA induced by sensitization and consequent provocation with HDM extracts.
  
  
  RESULTS
  HDM-derived β-glucans, rather than LPS, were proven to be essential to activating innate immunity in the nasal mucosa and triggering AR, which depended on Toll-like receptor 2 (TLR2), but not on TLR4; however, the LPS/TLR4 signaling axis, rather than β-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of β-glucans and LPS in inducing the surface expression of TLR2 and TLR4 and their translocation to lipid rafts in nasal and bronchial epithelial cells, respectively. We also showed that dual oxidase 2-generated reactive oxygen species mediate both β-glucan-induced TLR2 activation and LPS-induced TLR4 activation.
  
  
  CONCLUSIONS
  We describe a novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA, by showing the critical role of HDM-induced TLR activation via dual oxidase 2-mediated reactive oxygen species.
authors.affiliation: Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji-Hwan
authors.initials: JH
authors.lastname: Ryu
authors.forename: Jung-Yeon
authors.initials: JY
authors.lastname: Yoo
authors.forename: Min-Ji
authors.initials: MJ
authors.lastname: Kim
authors.forename: Sang-Gyu
authors.initials: SG
authors.lastname: Hwang
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Ahn
authors.forename: Jae-Chan
authors.initials: JC
authors.lastname: Ryu
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Choi
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Joo
authors.forename: Chang-Hoon
authors.initials: CH
authors.lastname: Kim
authors.forename: Sang-Nam
authors.initials: SN
authors.lastname: Lee
authors.forename: Won-Jae
authors.initials: WJ
authors.lastname: Lee
authors.forename: Jaesang
authors.initials: J
authors.lastname: Kim
authors.forename: Dong Min
authors.initials: DM
authors.lastname: Shin
authors.forename: Mi-Na
authors.initials: MN
authors.lastname: Kweon
authors.forename: Yun Soo
authors.initials: YS
authors.lastname: Bae
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
mesh_terms: D000818:Animals; D001249:Asthma / Q000276:immunology / Q000378:metabolism; D000074623:Dual Oxidases; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D019255:NADPH Oxidases / Q000276:immunology / Q000378:metabolism; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism; D039981:Pyroglyphidae / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D012137:Respiratory System / Q000276:immunology* / Q000378:metabolism; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D047071:beta-Glucans / Q000276:immunology / Q000378:metabolism
chemical_list: D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D047071:beta-Glucans; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C519130:Duox1 protein, mouse