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Updated: Jun 25, 2026
Analysis of Pulmonary Dendritic Cell Maturation and Migration during Allergic Airway Inflammation
Published on: July 23, 2012
Asthma-related environmental fungus, Alternaria, activates dendritic cells and produces potent Th2 adjuvant activity
Takao Kobayashi1, Koji Iijima, Suresh Radhakrishnan
1Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Abstract:
Asthma is thought to result from dysregulated Th2-like airway inflammatory responses to the environment. Although the etiology of asthma is not fully understood in humans, clinical and epidemiological evidence suggest a potential link between exposure to environmental fungi, such as Alternaria, and development and/or exacerbation of asthma. The goal of this project was to investigate the mechanisms of airway Th2 responses by using Alternaria as a clinically relevant model for environmental exposure. Airway exposure of naive animals to an experimental Ag, OVA, or a common allergen, short ragweed pollen, induced no or minimal immune responses to these Ags. In contrast, mice developed strong Th2-like immune responses when they were exposed to these Ags in the presence of Alternaria extract. Extracts of other fungi, such as Aspergillus and Candida, showed similar Th2 adjuvant effects, albeit not as potently. Alternaria stimulated bone marrow-derived dendritic cells (DCs) to express MHC class II and costimulatory molecules, including OX40 ligand, in vitro. Importantly, Alternaria inhibited IL-12 production by activated DCs, and DCs exposed to Alternaria enhanced Th2 polarization of CD4(+) T cells. Furthermore, adoptive airway transfer of DCs, which had been pulsed with OVA in the presence of Alternaria, showed that the recipient mice had enhanced IgE Ab production and Th2-like airway responses to OVA. Thus, the asthma-related environmental fungus Alternaria produces potent Th2-like adjuvant effects in the airways. Such immunogenic properties of certain environmental fungi may explain their strong relationships with human asthma and allergic diseases.
Insights
Environmental fungi like Alternaria can worsen asthma by boosting Th2-like immune responses. This study shows Alternaria acts as an adjuvant, enhancing airway inflammation and allergic reactions in mice.
Area of Science:
- Immunology
- Environmental Health
- Allergy Research
Background:
- Asthma pathogenesis involves dysregulated T helper 2 (Th2)-like airway inflammation.
- Environmental fungi, particularly Alternaria, are increasingly linked to asthma development and exacerbation.
- The precise mechanisms by which fungi influence allergic airway responses remain incompletely understood.
Purpose of the Study:
- To investigate the immunomodulatory mechanisms of environmental fungi, using Alternaria as a model.
- To determine if Alternaria can act as a Th2 adjuvant in airway allergic responses.
- To elucidate the role of Alternaria-exposed dendritic cells (DCs) in T cell polarization.
Main Methods:
- Mice were exposed to allergens (OVA, ragweed) with or without fungal extracts (Alternaria, Aspergillus, Candida).
- Bone marrow-derived dendritic cells (DCs) were stimulated with Alternaria in vitro to assess surface molecule expression and cytokine production (IL-12).
- OVA-pulsed DCs, pre-treated with Alternaria, were adoptively transferred to recipient mice to evaluate airway immune responses.
Main Results:
- Alternaria extract significantly enhanced Th2-like immune responses to allergens in mice, unlike other fungi tested.
- Alternaria stimulated DCs to upregulate MHC class II and costimulatory molecules (OX40 ligand) and inhibited IL-12 production.
- DCs exposed to Alternaria promoted Th2 polarization of CD4(+) T cells and led to increased IgE antibody production in recipient mice.
Conclusions:
- The environmental fungus Alternaria exhibits potent Th2-like adjuvant properties in the airways.
- Alternaria's ability to modulate DC function and promote Th2 responses contributes to its association with asthma.
- These findings highlight the immunogenic potential of environmental fungi in allergic airway diseases.
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