A study conducted by scientists from the Institut Pasteur has revealed that microbes protect the lungs from subsequently developing allergies and asthma. This long-term protection is "memorized" not by immune system cells but by fibroblasts, structural cells in the lungs. These results, published in Nature Immunology , open up new possibilities for the development of preventive strategies for respiratory allergies.
The constant rise in respiratory allergies and asthma in industrialized countries raises the question of why some people develop allergies while others do not. One theory is that exposure to microbes prevents this phenomenon, but the underlying mechanism had never been identified.
Scientists from the Institut Pasteur and Inserm, led by Gérard Eberl, Head of the Microenvironment and Immunity Unit, and Lucie Peduto, Head of the Stroma, Inflammation and Tissue Repair Unit, wanted to test this theory directly. They made a remarkable discovery: when the lungs are exposed to microbe fragments, a lasting immune memory is induced that effectively blocks subsequent allergic reactions for several months.
A decisive experiment reveals long-lasting protection
The scientists exposed the lungs of mice to fragments of viruses or bacteria, triggering a type 1 immune response – the body's natural response to these microbes. When the mice were exposed to an allergen at the same time, they were fully protected against it for at least six weeks.
The scientists also discovered that pre-exposing the mice to microbe fragments gave them lasting protection from subsequent reactions for more than three months. In the absence of this initial protection, the mice developed a strong reaction characterized by an accumulation of eosinophils, a type of immune cell, in the lungs. Without the protection induced by microbe fragments, initial exposure to the allergen "programmed" the lungs to hypersensitivity, and in the event of re-exposure the allergic reaction was drastically exacerbated.
Fibroblasts, unexpected players in immune memory
Where was this protective memory stored? Although the cells usually associated with the immune system – B and T cells – have long been considered the main protagonists in immune memory, a detailed analysis of the lung cells revealed that fibroblasts play a key role.
"The originality of our findings lies in the nature of this immune memory, the fact that it comes not from immune system cells but from structural cells in the lungs known as fibroblasts," explains Lucie Peduto.
Fibroblasts are "ordinary" cells that form the structure of the lungs, contribute to tissue repair, and support and direct immune cells. So what equips them to play this role? The answer is an epigenetic modification in the Ccl11 gene that encodes the molecule CCL11, or eotaxin, responsible for recruiting eosinophils – key effectors of allergic reactions.
"In mice, we observed that when the lungs trigger a type 1 immune response, induced by viruses or bacteria, the Ccl11 gene in the fibroblasts is blocked for a lengthy period. This epigenetic modification lasts for months and fully protects the lungs from allergic reactions, representing a form of tissue memory that lasts well after the immune cells present during the initial infection have gone," explains Amy Blondeau, a scientist in the Institut Pasteur's Microenvironment and Immunity Unit and co-first author of the study.
Implications for allergy prevention
This discovery opens up several clinical avenues.
First, it justifies the use of prophylaxis. Early administration of agents that stimulate a type 1 immune response (like OM-85, already used in clinical practice) could offer lasting prevention against the development of allergies. This would be an effective prevention strategy rather than just a symptomatic treatment.
Second, the study suggests that rather than concentrating solely on the immune system, fibroblasts could represent a therapeutic target. Future therapies could directly correct the epigenetic programming of fibroblasts to protect against allergens.
The team is continuing to explore ways of converting this major discovery into therapeutic approaches by attempting to answer some remaining questions. In children, how long might this infection-induced allergy protection last? What is the best way of inducing this protection? Can protective memory be restored in individuals who already suffer from allergies?
Long-term inhibition of protease hypersensitivity by initial immunological cross-regulation and epigenetic memory in lung stromal cells , Nature Immunology , March 3, 2026
Jaechan Ryu 1,7,8 , Amy Blondeau 1,4,7 , Olivier Mirabeau 2 , Selene Di Carlo 3 , Victoire Baillet 2 , David Hardy 5 , Christian Pasquali 6 , Lucie Peduto 3,8 , Gérard Eberl 1,8
Nature Immunology
Experimental study
Long-term inhibition of protease hypersensitivity by initial immunological cross-regulation and epigenetic memory in lung stromal cells
3-Mar-2026