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Updated: Oct 21, 2025
Murine Model of Allergen Induced Asthma
Published on: May 14, 2012
Novel Mouse Models of Fungal Asthma
Michael Daines1,2, Rhea Pereira1, Aubrey Cunningham1
1Department of Pediatrics, College of Medicine, University of Arizona, Tucson, AZ, United States.
Abstract:
Alternaria alternata is a ubiquitous fungus and a major allergen associated with the development of asthma. Inhalation of intact spores is the primary cause of human exposure to fungal allergen. However, allergen-rich cultured fungal filtrates are oftentimes used in the current models of fungal sensitization that do not fully reflect real-life exposures. Thus, establishing novel spore exposure models is imperative. In this study, we established novel fungal exposure models of both adult and neonate to live spores. We examined pathophysiological changes in the spore models as compared to the non-exposure controls and also to the conventional filtrate models. While both Alternaria filtrate- and spore-exposed adult BALB/c mice developed elevated airway hyperresponsiveness (AHR), filtrates induced a greater IgE mediated response and higher broncholavage eosinophils than spores. In contrast, the mice exposed to Alternaria spores had higher numbers of neutrophils. Both exposures induced comparable levels of lung tissue inflammation and mucous cell metaplasia (MCM). In the neonatal model, exposure to Alternaria spores resulted in a significant increase of AHR in both adult and neonatal mice. Increased levels of IgE in both neonatal and adult mice exposed to spores was associated with increased eosinophilia in the treatment groups. Adult demonstrated increased numbers of lymphocytes that was paralleled by increased IgG1 production. Both adults and neonates demonstrated similarly increased eosinophilia, IgE, tissue inflammation and MCM.
Insights
This study introduces new models for Alternaria alternata spore exposure, revealing distinct immune responses compared to traditional filtrate models. Spore exposure is crucial for understanding real-world fungal allergy development.
Area of Science:
- Immunology
- Allergology
- Environmental Health
Background:
- Alternaria alternata is a common fungus and a significant allergen linked to asthma.
- Current fungal sensitization models often use fungal filtrates, which don't fully represent real-world exposure to intact spores.
- Novel models are needed to accurately study the effects of fungal spore inhalation.
Purpose of the Study:
- To establish and evaluate novel exposure models using live Alternaria alternata spores in adult and neonatal mice.
- To compare the pathophysiological changes induced by spore exposure with those from conventional filtrate models and controls.
- To investigate the impact of spore exposure on airway hyperresponsiveness, immune cell infiltration, and lung pathology.
Main Methods:
- Development of novel exposure models for adult and neonatal mice using live Alternaria alternata spores.
- Comparison of immune responses (IgE, IgG1, eosinophils, neutrophils, lymphocytes) and lung pathology (inflammation, mucous cell metaplasia) between spore-exposed, filtrate-exposed, and control groups.
- Assessment of airway hyperresponsiveness (AHR) in exposed mice.
Main Results:
- Both filtrate and spore exposure in adult mice induced elevated airway hyperresponsiveness (AHR).
- Filtrates led to higher IgE and eosinophils, while spores increased neutrophil counts in adult mice.
- Spore exposure in both adult and neonatal mice significantly increased AHR, IgE, eosinophilia, and lung tissue inflammation.
Conclusions:
- Novel models using live Alternaria alternata spores provide a more relevant approach to studying fungal sensitization.
- Spore exposure elicits distinct immune responses compared to filtrate exposure, particularly in neonatal models.
- These findings highlight the importance of spore inhalation in the development of allergic airway diseases.
