New Insights into Mold Proteins Causing Airway Allergies

Recent research from the National Institute of Biological Sciences in Beijing has shed light on how specific proteins produced by the mold Alternaria alternata contribute to allergic airway inflammation. Scientists have identified two pore-forming proteins, Aeg-S and Aeg-L, that work together to pierce the membranes of airway epithelial cells. These proteins form ring-shaped drills that disrupt cellular integrity when inhaled, leading to calcium influx and activation of intracellular signaling pathways like MAPK. This disruption prompts the release of IL-33, an alarm cytokine that signals immune system activation and sustains inflammatory responses.

The study employed human lung epithelial cell models and mouse models to simulate allergen exposure. It was observed that low levels of these mold proteins cause calcium entry and messenger activation, while higher levels cause cell bursting and IL-33 release. Interestingly, neither protein acts alone to cause these effects; they require their combined action to perforate membranes.

Further experiments demonstrated that blocking calcium entry or inhibiting MAPK signaling prevented downstream inflammatory reactions. In mice, inhalation of the protein duo triggered classic allergy symptoms, including increased eosinophils, T-helper-2 cells, and IgE production. Conversely, fungal strains lacking either protein failed to induce these responses, indicating their crucial role.

The research suggests that the ability of these proteins to perforate cell membranes acts as a danger signal, initiating type 2 immune pathways. The findings propose that many allergens and venoms containing pore-forming proteins may utilize this mechanism to provoke airway inflammation, offering new avenues for targeted allergy therapies.

This groundbreaking work highlights the significance of membrane perforation as a key trigger in allergic responses, broadening our understanding of airway allergy pathogenesis and potential intervention points.

Source: https://medicalxpress.com/news/2025-08-membrane-drilling-mold-protein-duo.html