A 4-Week Model of House Dust Mite (HDM) Induced Allergic Airways Inflammation with Airway Remodeling

Abstract

Animal models of allergic airways inflammation are useful tools in studying the pathogenesis of asthma and potential therapeutic interventions. The different allergic airways inflammation models available to date employ varying doses, frequency, duration and types of allergen, which lead to the development of different features of asthma; showing varying degrees of airways inflammation and hyper-responsiveness (AHR) and airways remodeling. Models that also exhibit airway remodeling, a key feature of asthma, in addition to AHR and airway inflammation typically require 5–12 weeks to develop. In this report, we describe a 4-week mouse model of house dust mite (HDM)-induced allergic airways inflammation, and compare the phenotypic features of two different doses of HDM exposures (10 µg and 25 µg) for 5 days/week with a well-characterized 8-week chronic HDM model. We found that 4 weeks of intranasal HDM (25 µg in 35 µl saline; 5 days/week) resulted in AHR, airway inflammation and airway remodeling that were comparable to the 8-week model. We conclude that this new 4-week HDM model is another useful tool in studies of human asthma that offers advantages of shorter duration for development and decreased costs when compared to other models that require longer durations of exposure (5–12 weeks) to develop.

Chronic, Elevated Maternal Corticosterone During Pregnancy in the Mouse Increases Allergic Airway Inflammation in Offspring

“…Alternatively, while heightened serum IgE is certainly a hallmark of TH2 immune responses, it is not strongly predictive of TH2 signatures in tissues or asthma development in patients (2). Furthermore, it was previously demonstrated that asthma induction protocols require at least 4 weeks of HDM sensitization to induce heightened IgE in serum, which explains why our shorter induction protocol did not result in increased serum IgE (47). Therefore, our results are in accordance with the immune-related phenotypes that were previously characterized (33), and while we did not perform methacholine sensitivity assays, the inflammatory profile observed is suggestive of an allergic asthma phenotype in the lung.…”

Role of Inflammatory Risk Factors in the Pathogenesis of Streptococcus pneumoniae

“…Additionally, dysregulation of the IL-17F/IL-17RC axis has been shown to predispose allergic inflammation in murine models of fungal allergic asthma ( 82 ). Besides murine models of fungal allergic asthma, mouse models using the house dust mite (HDM) also feature similarities to human allergic asthma, including eosinophilic lung inflammation and cytokines primarily associated with Th2-type inflammation ( 83 ). These animal models are used for evaluating the efficacy of anti-asthma drugs and exacerbations of bacterial/viral infections.…”

In utero ultrafine particulate matter exposure causes offspring pulmonary immunosuppression

“…Th17 cells can exacerbate Th2-cell–mediated eosinophilic inflammation as well as promote airway neutrophilia. The house dust mite (HDM) asthma model primes a strong Th17 response resulting in enhanced pulmonary inflammation and airway hyperresponsiveness (15).…”