Allergens May Make Us Cough and Sneeze by Poking Holes in Airway Cells
The immune system senses damage to cell membranes caused by pore-forming proteins and mounts a response
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The sneezing, itchy eyes and coughing elicited by some allergens are caused by proteins creating holes in airway cells, reports a study published this week in Nature.
The findings challenge scientists’ understanding of how allergies are triggered, says Feargal Ryan, who studies host–microbe interactions at Flinders University in Adelaide, Australia. Before this, the mechanism that triggers immune responses to allergens was not really understood. Researchers focused mostly on how a single allergen elicits a reaction, rather than looking for a generalizable mechanism.
The results could also change allergy-treatment strategies, which typically target the allergen directly or downstream immune responses. Now, researchers can start looking for ways to target the hole-creating proteins that are initiating the immune response, Ryan says.
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Pore-forming proteins
Researchers based in Beijing, China, identified two proteins in the mould Alternaria alternata, which causes allergic reactions in about 5% of people, that trigger the airway inflammation seen during allergic reactions.
Together, the proteins, called Aeg-S and Aeg-L, create a pore in the membranes of cells lining the nose, throat and lungs. This allows calcium ions to enter the cells and release molecules that alert the immune system to danger. The damage to cell membranes from these pore-forming proteins could be a “common signal that our body uses to recognize something as an allergen”, says co-author Mo Xu, who studies immune responses at Tsinghua University.
To test how the proteins stimulated the immune system, the team treated lung cells with the proteins. Administering the proteins at the same time triggered a similar response as administering an extract of A. alternata, but this response was not seen when the proteins were given one at a time.
The researchers also tested whether the proteins could cause an allergic airway inflammation in mice. Six hours after mice were given the proteins intranasally, the rodents showed immune responses similar to those triggered by exposure to A. alternata.
The team also observed signs that the mice had developed a respiratory allergy, such as increased levels of serum immunoglobulin E (IgE) — an antibody produced in response to allergens — after the mice were given the proteins every three days for two weeks. This response wasn’t seen when the proteins were administered separately, or when mice were exposed to genetically modified mould lacking either protein.
Common trigger
The team suspected that other allergens with pore-forming proteins would also induce an immune response. When the researchers exposed mice to pore-forming proteins from the airborne mould Aspergillus niger — an allergen — and the venom of the sea anemone Actinia equina, they observed an immune response similar to that induced by Aeg-S and Aeg-L. They also found that allergic airway inflammation was triggered by pore-forming proteins from the earthworm Eisenia fetida, the king oyster mushroom Pleurotus eryngii, the bacterium Clostridium perfringens and the fungus Laetiporus sulphureus.
The findings suggest that allergens that are unrelated to each other can trigger allergic reactions in the same way, because they have pore-forming proteins that have been conserved by evolution, says Ryan. “This is a new way of thinking about allergens,” he says. Future treatments could look at whether there’s a way to block or inactivate those proteins and stop the reactions, he adds.
Xu says his team are investigating which immune-response pathways are activated after pore-forming proteins damage cell membranes, and whether allergens with proteins that don’t form pores, such as those in dust mites or pollens, use the same pathway.
This article is reproduced with permission and was first published on July 31, 2025.
