Journal ArticleDOI
Distinct TLR-mediated pathways regulate house dust mite–induced allergic disease in the upper and lower airways
Ji-Hwan Ryu,Jung Yeon Yoo,Min-Ji Kim,Sang Gyu Hwang,Kwang Chul Ahn,Jae Chan Ryu,Mi Kyung Choi,Jung Hee Joo,Chang Hoon Kim,Sang Nam Lee,Won-Jae Lee,Jaesang Kim,Dong Min Shin,Mi-Na Kweon,Yun Soo Bae,Joo-Heon Yoon +15 more
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TLDR
A novel finding of distinctive innate immunity of the nose and lungs, respectively, which trigger AR and AA is described, by showing the critical role of HDM-induced TLR activation via dual oxidase 2-mediated reactive oxygen species.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.read more
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Journal ArticleDOI
Allergens and the airway epithelium response: Gateway to allergic sensitization
Bart N. Lambrecht,Hamida Hammad +1 more
TL;DR: Lung epithelial cells recognize allergens through expression of pattern recognition receptors and mount an innate immune response driven by activation of nuclear factor κB, which is crucial in determining the outcome of allergen inhalation.
Journal ArticleDOI
TLR-Dependent Human Mucosal Epithelial Cell Responses to Microbial Pathogens.
Ryan McClure,Paola Massari +1 more
TL;DR: The mechanisms by which TLR signaling is regulated in mucosal epithelial cells include differential expression and levels of TLRs, their cellular localization and positioning within the tissue in a fashion that favors responses to pathogens while dampening responses to commensals and maintaining tissue homeostasis in physiologic conditions.
Journal ArticleDOI
Skin exposure promotes a Th2-dependent sensitization to peanut allergens
Leticia Tordesillas,Ritobrata Goswami,Sara Benedé,Galina Grishina,David Dunkin,Kirsi M. Järvinen,Soheila J. Maleki,Hugh A. Sampson,M. Cecilia Berin +8 more
TL;DR: The hypothesis that peanuts are allergenic due to inherent adjuvant activity is supported and it is suggested that skin exposure to food allergens contributes to sensitization to foods in early life.
Journal ArticleDOI
Role of DUOX in gut inflammation: lessons from Drosophila model of gut-microbiota interactions
Sung-Hee Kim,Won-Jae Lee +1 more
TL;DR: Genetic studies on the Drosophila DUOX system and on gut-associated bacteria with a distinct ability to activate DUOX may provide critical information related to the homeostatic inflammation as well as etiology of chronic inflammatory diseases, which will enhance understanding on the mucosal inflammatory diseases frequently observed in the microbe-contacting epithelia of humans.
Journal ArticleDOI
The Role of Dust Mites in Allergy.
TL;DR: Beyond their direct importance as a major allergen source, an understanding of dust mites leads to insights into the nature of atopy and of allergic sensitization in general.
References
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Journal ArticleDOI
Collaborative Induction of Inflammatory Responses by Dectin-1 and Toll-like Receptor 2
TL;DR: This report examines how dectin-1, a lectin family receptor for β-glucans, collaborates with TLRs in recognizing microbes and demonstrates that collaborative recognition of distinct microbial components by different classes of innate immune receptors is crucial in orchestrating inflammatory responses.
Journal ArticleDOI
House dust mite allergen induces asthma via Toll-like receptor 4 triggering of airway structural cells.
Hamida Hammad,Marcello Chieppa,Frédéric Perros,Monique Willart,Ronald N. Germain,Bart N. Lambrecht,Bart N. Lambrecht +6 more
TL;DR: It is shown in irradiated chimeric mice that Toll-like receptor 4 expression on radioresistant lung structural cells, but not on DCs, is necessary and sufficient for DC activation in the lung and for priming of effector T helper responses to HDM.
Journal ArticleDOI
Dectin-1 is required for beta-glucan recognition and control of fungal infection.
Philip R. Taylor,S. Vicky Tsoni,Janet A. Willment,Kevin M. Dennehy,Marcela Rosas,Helen Findon,Ken Haynes,Chad Steele,Marina Botto,Siamon Gordon,Gordon D. Brown +10 more
TL;DR: It is shown that deficiency of dectin-1, the myeloid receptor for β-glucan, rendered mice susceptible to infection with Candida albicans, and a signaling non–Toll-like pattern-recognition receptor required for the induction of protective immune responses is established.
Journal ArticleDOI
Analysis of the Lung Microbiome in the “Healthy” Smoker and in COPD
John R. Erb-Downward,Deborah L. Thompson,MeiLan K. Han,Christine M. Freeman,Christine M. Freeman,Lisa McCloskey,Lisa McCloskey,Lindsay A. Schmidt,Vincent B. Young,Galen B. Toews,Galen B. Toews,Jeffrey L. Curtis,Jeffrey L. Curtis,Baskaran Sundaram,Fernando J. Martinez,Gary B. Huffnagle +15 more
TL;DR: The data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas within the same lung of subjects with advanced COPD.
Journal ArticleDOI
Allergenicity resulting from functional mimicry of a Toll-like receptor complex protein
Aurelien Trompette,Senad Divanovic,Alberto Visintin,Carine Blanchard,Rashmi S. Hegde,Rajat Madan,Peter S. Thorne,Marsha Wills-Karp,Theresa L. Gioannini,Jerry P. Weiss,Christopher L. Karp +10 more
TL;DR: The results indicate that Der p 2 tends to be targeted by adaptive immune responses because of its auto-adjuvant properties, suggesting that intrinsic adjuvant activity by such proteins and their accompanying lipid cargo may have some generality as a mechanism underlying the phenomenon of allergenicity.