Allergic Airway Responses to Fungal Allergens

Fungal spores and fragments abound in both indoor and outdoor environments and represent a major class of aeroallergens implicated in asthma, allergic rhinitis and chronic rhinosinusitis. Common sensitising species include Aspergillus, Alternaria, Cladosporium and Penicillium, which, upon inhalation, penetrate the airway mucosa and interact with epithelial cells, dendritic cells and resident innate lymphoid cells. Fungal proteases and cell-wall components activate pattern recognition receptors and protease-activated receptors on epithelial surfaces, leading to the release of alarmins such as IL-33, IL-25 and thymic stromal lymphopoietin. These cytokines orchestrate a type 2 immune cascade, recruiting eosinophils, mast cells and Th2 lymphocytes to the bronchial submucosa. Protease-mediated disruption of epithelial junctions further enhances allergen penetration, while allergen-derived enzymes can degrade the extracellular matrix and directly stimulate airway smooth muscle cells, driving hyperresponsiveness and bronchoconstriction. Genetic predisposition, environmental factors such as humidity and urbanisation, and comorbidities including atopic dermatitis and existing asthma all modulate individual susceptibility. Clinically, fungal sensitisation correlates with disease severity, exacerbation frequency and treatment resistance. Ongoing research seeks to elucidate the molecular basis of fungal allergenicity, refine diagnostic sIgE profiling and develop targeted therapies that interrupt key protease- or cytokine-driven pathways.

Research from Nature Portfolio

Investigations into a major Aspergillus fumigatus allergen, the serine protease Alp 1, have revealed its capacity to infiltrate the bronchial submucosa and locally degrade extracellular matrix components. This proteolytic activity alters airway smooth muscle cell–matrix contacts, elevating RhoA-dependent calcium sensitivity and precipitating exaggerated bronchoconstriction. By demonstrating that Alp 1 alone can induce airway hyperresponsiveness through direct smooth muscle modulation, this work establishes a mechanistic link between inhaled fungal proteases and the pathophysiology of severe, treatment-resistant asthma.

Allergic Airway Responses to Fungal Allergens publication trend

The graph below shows the total number of articles in allergic airway responses to fungal allergens across all publications each year (not limited to Nature Index journals).

Technical terms

Type 2 immunity: A coordinated immune response involving IL-4, IL-5 and IL-13 that promotes eosinophilia, IgE production and mucous hypersecretion.

Protease-activated receptor (PAR): A cell-surface receptor cleaved and activated by proteases, triggering intracellular signalling cascades.

Airway hyperresponsiveness: Increased sensitivity and constriction of bronchial smooth muscle in response to stimuli.

Alarmins: Epithelial-derived cytokines (e.g. IL-33, IL-25, TSLP) that initiate and amplify type 2 inflammation.

Innate lymphoid cells (ILC2): Tissue-resident innate immune cells producing type 2 cytokines in response to epithelial alarmins.

References

1. Fungal allergen sensitization: Prevalence, risk factors, and geographic variation in the United States. Journal of Allergy and Clinical Immunology (2023).
2. Novel mechanistic insights underlying fungal allergic inflammation. PLOS Pathogens (2023).
3. Immunopathologic Role of Fungi in Chronic Rhinosinusitis. International Journal of Molecular Sciences (2023).
4. A fungal protease allergen provokes airway hyper-responsiveness in asthma. Nature Communications (2015).
5. Airway Epithelium Interactions with Aeroallergens: Role of Secreted Cytokines and Chemokines in Innate Immunity. Frontiers in Immunology (2015).
6. Barrier Disrupting Effects of Alternaria Alternata Extract on Bronchial Epithelium from Asthmatic Donors. PLOS ONE (2013).