Mechanisms of allergy and clinical immunologyDistinct TLR-mediated pathways regulate house dust mite–induced allergic disease in the upper and lower airways
Section snippets
Methods
For details on methods, see this article's Methods section (in the Online Repository available at www.jacionline.org).
β-Glucans and LPS within HDM-triggered innate immunity in the upper and lower airways, respectively
Because β-glucans and LPS are known to be the main PAMPs within HDM extracts that activate innate immunity in the airway epithelium,13, 17, 19, 22 we examined their roles in the HDM-induced innate immune responses in airway epithelial cells. We pretreated HDM extracts with either β-glucanase to degrade β-glucan structures (HDMΔβ-glucan) or polymyxin B to inactivate LPS (HDMΔLPS) before treating primary normal human nasal epithelial (NHNE) cells. First, we measured the level of CCL20 secretion
Discussion
Here, we clearly showed that HDM-derived β-glucans and TLR2 were critical for activating innate immunity in the nasal mucosa and subsequent AR by showing that CCL20 secretion, DC recruitment, and HDM-induced AR were attenuated in HDMΔβ-glucan challenge or TLR2−/− mice. In contrast, LPS/TLR4 signaling axis, rather than β-glucan/TLR2, played a pivotal role in activating innate immunity in the lung mucosa and resultant AA in our study, in agreement with previous studies that TLR4, rather than
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Supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (grant 2012-0000803 to J.-H.Y. and grant 2010-0022899 to J.-H.R.) and by the Yonsei University College of Medicine (grant 6-2009-0115 to J.-H.R.). None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
Disclosure of potential conflict of interest: J.-H. Ryu has received grants from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology and Yonsei University College of Medicine. J.-H. Yoon has received grants from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science, and Technology. The rest of the authors declare that they have no relevant conflicts of interest.