Allergens Might Make Us Cough and Sneeze by Poking Holes in Airway Cells
The immune system senses harm to cell membranes attributable to pore-forming proteins and mounts a response
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The sneezing, itchy eyes and coughing elicited by some allergens are attributable to proteins creating holes in airway cells, stories a research printed this week in Nature.
The findings problem scientists’ understanding of how allergy symptoms are triggered, says Feargal Ryan, who research host–microbe interactions at Flinders College in Adelaide, Australia. Earlier than this, the mechanism that triggers immune responses to allergens was probably not understood. Researchers centered totally on how a single allergen elicits a response, quite than in search of a generalizable mechanism.
The outcomes might additionally change allergy-treatment methods, which generally goal the allergen instantly or downstream immune responses. Now, researchers can begin in search of methods to focus on the hole-creating proteins which can be initiating the immune response, Ryan says.
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Pore-forming proteins
Researchers primarily based in Beijing, China, recognized two proteins within the mould Alternaria alternata, which causes allergic reactions in about 5% of individuals, that set off the airway irritation seen throughout allergic reactions.
Collectively, the proteins, known as Aeg-S and Aeg-L, create a pore within the membranes of cells lining the nostril, throat and lungs. This enables calcium ions to enter the cells and launch molecules that alert the immune system to hazard. The harm to cell membranes from these pore-forming proteins may very well be a “widespread sign that our physique makes use of to acknowledge one thing as an allergen”, says co-author Mo Xu, who research immune responses at Tsinghua College.
To check how the proteins stimulated the immune system, the crew handled lung cells with the proteins. Administering the proteins on the identical time triggered an analogous response as administering an extract of A. alternata, however this response was not seen when the proteins got one after the other.
The researchers additionally examined whether or not the proteins might trigger an allergic airway irritation in mice. Six hours after mice got the proteins intranasally, the rodents confirmed immune responses much like these triggered by publicity to A. alternata.
The crew additionally noticed indicators that the mice had developed a respiratory allergy, similar to elevated ranges of serum immunoglobulin E (IgE) — an antibody produced in response to allergens — after the mice got the proteins each three days for 2 weeks. This response wasn’t seen when the proteins have been administered individually, or when mice have been uncovered to genetically modified mould missing both protein.
Frequent set off
The crew suspected that different allergens with pore-forming proteins would additionally induce an immune response. When the researchers uncovered mice to pore-forming proteins from the airborne mould Aspergillus niger — an allergen — and the venom of the ocean anemone Actinia equina, they noticed an immune response much like that induced by Aeg-S and Aeg-L. Additionally they discovered that allergic airway irritation 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 counsel that allergens which can be unrelated to one another can set off allergic reactions in the identical manner, as a result of they’ve pore-forming proteins which were conserved by evolution, says Ryan. “This can be a new mind-set about allergens,” he says. Future therapies might take a look at whether or not there’s a option to block or inactivate these proteins and cease the reactions, he provides.
Xu says his crew are investigating which immune-response pathways are activated after pore-forming proteins harm cell membranes, and whether or not allergens with proteins that don’t type pores, similar to these in mud mites or pollens, use the identical pathway.
This text is reproduced with permission and was first printed on July 31, 2025.
