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Role of particulate antigens of Aspergillus in murine eosinophilia
V P Kurup1, H Choi, P S Murali
1Department of Medicine, Medical College of Wisconsin, Milwaukee, USA.
Objective:
Allergic bronchopulmonary aspergillosis, a disabling hypersensitivity lung disease, results from inhalation of Aspergillus fumigatus antigens present in contaminated environments. A murine model has been developed to understand the immune mechanism involved in allergic bronchopulmonary aspergillosis. We have investigated the immunoregulatory role of different physical forms of A.fumigatus antigens, such as A.fumigatus spores, soluble antigens. and soluble antigen coupled inert particles, in the model.
Methods:
BALB/c mice were exposed to soluble A.fumigatus antigens, spores, or inert particles of comparable size to the spores coupled with A.fumigatus soluble antigens. Antibody and eosinophil response, pulmonary pathology, and cytokine expressions were studied.
Results:
Peripheral blood eosinophilia and pulmonary inflammation with influx of eosinophils into the lung was detected more in animals exposed to particulate antigens than in those exposed to soluble antigen. However, the total serum IgE and Aspergillus-specific IgG levels showed only a slight increase in the former groups as opposed to elevated levels in animals exposed to soluble antigen. The cytokine expression in in vitro antigen stimulated spleen cells showed a typical Th2 pattern in all antigen-exposed animals. IL-5 mRNA could be detected in the spleen cells cultured with antigen from all groups of antigen-exposed animals.
Conclusion:
Particulate A.fumigatus antigens induced eosinophilia in mice prior to the elevation of serum IgE levels. This pattern of IgE and eosinophilia is reversed with the soluble antigen exposure in this model.
Insights
Particulate Aspergillus fumigatus antigens trigger eosinophilia before IgE elevation in mice, unlike soluble antigens which reverse this pattern. This finding aids understanding of allergic bronchopulmonary aspergillosis immune responses.
Area of Science:
- Immunology
- Allergology
- Pulmonary Medicine
Background:
- Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by Aspergillus fumigatus.
- Understanding the immune mechanisms of ABPA is crucial for developing effective treatments.
- A murine model is utilized to study the immune response to A. fumigatus.
Purpose of the Study:
- To investigate the immunoregulatory role of different physical forms of A. fumigatus antigens in a murine model.
- To compare the effects of particulate (spores, antigen-coupled particles) versus soluble A. fumigatus antigens on immune responses.
Main Methods:
- BALB/c mice were exposed to A. fumigatus spores, soluble antigens, or soluble antigen coupled to inert particles.
- Immune responses including antibody levels, eosinophilia, pulmonary pathology, and cytokine expression were analyzed.
Main Results:
- Particulate A. fumigatus antigens induced greater peripheral blood eosinophilia and pulmonary inflammation compared to soluble antigens.
- Serum IgE and Aspergillus-specific IgG levels were elevated with soluble antigen exposure, but only slightly increased with particulate antigens.
- Cytokine expression analysis revealed a Th2 pattern, with IL-5 mRNA detected in spleen cells from all antigen-exposed groups.
Conclusions:
- Particulate A. fumigatus antigens promote eosinophilia preceding IgE elevation in this model.
- Soluble antigen exposure demonstrated a reversed pattern, with IgE elevation preceding eosinophilia.
- These findings highlight the distinct immunomodulatory effects of different antigen forms in ABPA pathogenesis.