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Updated: Feb 15, 2026
Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
Time-dependent distinct roles of Toll-like receptor 4 in a house dust mite-induced asthma mouse model
T Ishii1,2, Y Niikura1, K Kurata3
1Department of Pharmacotherapy, Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo, Japan.
Abstract:
House dust mites (HDMs) are a common source of allergens that trigger both allergen-specific and innate immune responses in humans. Here, we examined the effect of allergen concentration and the involvement of Toll-like receptor 4 (TLR4) in the process of sensitization to house dust mite allergens in an HDM extract-induced asthma mouse model. Intranasal administration of HDM extract induced an immunoglobulin E response and eosinophilic inflammation in a dose-dependent manner from 2.5 to 30 μg/dose. In TLR4-knockout mice, the infiltration of eosinophils and neutrophils into the lung was decreased compared with that in wild-type mice in the early phase of inflammation (total of three doses). However, in the late phase of inflammation (total of seven doses), eosinophil infiltration was significantly greater in TLR4-knockout mice than in wild-type mice. This suggests that the roles of TLR4 signaling are different between the early phase and the later phase of HDM allergen-induced inflammation. Thus, innate immune response through TLR4 regulated the response to HDM allergens, and the regulation was altered during the phase of inflammation.
Insights
House dust mite (HDM) allergens trigger immune responses. Toll-like receptor 4 (TLR4) plays a dual role in HDM-induced asthma, initially reducing inflammation but increasing it later, suggesting complex regulation.
Area of Science:
- Immunology
- Allergology
- Respiratory Medicine
Background:
- House dust mites (HDMs) are significant allergens triggering immune responses.
- Understanding the mechanisms of HDM sensitization is crucial for asthma management.
- Toll-like receptor 4 (TLR4) is implicated in innate immune responses to various stimuli.
Purpose of the Study:
- To investigate the impact of HDM allergen concentration on sensitization.
- To elucidate the role of Toll-like receptor 4 (TLR4) in HDM-induced asthma.
- To differentiate the early and late phase involvement of TLR4 in allergic inflammation.
Main Methods:
- An HDM extract-induced asthma mouse model was utilized.
- Intranasal administration of varying HDM extract doses (2.5–30 μg/dose).
- Comparison of immune responses (IgE, eosinophils, neutrophils) in wild-type and TLR4-knockout mice.
Main Results:
- HDM extract induced a dose-dependent immunoglobulin E (IgE) response and eosinophilic inflammation.
- TLR4-knockout mice showed reduced early-phase lung inflammation (eosinophils, neutrophils).
- TLR4-knockout mice exhibited significantly greater late-phase eosinophil infiltration compared to wild-type mice.
Conclusions:
- HDM allergen concentration influences sensitization and allergic inflammation.
- TLR4 signaling plays a complex, phase-dependent role in HDM-induced asthma.
- Innate immune responses mediated by TLR4 are dynamically regulated during allergic inflammation.
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