Distinct TLR-mediated pathways regulate house dust mite-induced allergic disease in the upper and lower airways

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:131

Article

Ryu, Ji-Hwan^1,2  Yoo, Jung-Yeon³  Kim, Min-Ji^1,2  Hwang, Sang-Gyu¹  Ahn, Kwang Chu¹  Ryu, Jae-Chan^1,2  Choi, Mi-Kyung³  Joo, Jung Hee¹  Kim, Chang-Hoon^4,5  Lee, Sang-Nam¹  Lee, Won-Jae^6,7  Kim, Jaesang³  Shin, Dong Min⁸  Kweon, Mi-Na⁹  Bae, Yun Soo³  Yoon, Joo-Heon^1,2,4,5 

[1] Res Ctr Human Nat Def Syst, Seoul, South Korea

[2] Yonsei Univ, Coll Med, Brain Korea Project Med Sci 21, Seoul 120752, South Korea

[3] Ewha Womans Univ, Dept Life Sci, Seoul, South Korea

[4] Yonsei Univ, Coll Med, Dept Otorhinolaryngol, Seoul 120752, South Korea

[5] Yonsei Univ, Coll Med, Airway Mucus Inst, Seoul 120752, South Korea

[6] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea

[7] Natl Creat Res Initiat Ctr Symbiosyst, Seoul, South Korea

[8] Yonsei Univ, Coll Dent, Dept Oral Biol, Seoul 120752, South Korea

[9] Int Vaccine Inst, Div Sci Lab, Mucosal Immunol Sect, Seoul, South Korea

关键词: Allergic rhinitis;    allergic asthma;    innate immunity;    house dust mite;    pathogen associated molecular pattern;    beta-glucans;    Toll-like receptor;    epithelium;    reactive oxygen species;    dual oxidase 2;   

DOI  :  10.1016/j.jaci.2012.07.050

来源: Elsevier

【 摘 要 】

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 beta-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 beta-glucans/TLR2, was critical to HDM-induced AA. These differences were attributed to the specific role of beta-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 beta-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. (J Allergy Clin Immunol 2013;131:549-61.)

【 授权许可】

Free